ClinVar Genomic variation as it relates to human health
NM_025077.4(TOE1):c.-45G>A
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(1); Benign(8)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_025077.4(TOE1):c.-45G>A
Variation ID: 138310 Accession: VCV000138310.38
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45340208 (GRCh38) [ NCBI UCSC ] 1: 45805880 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 2, 2016 May 1, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_025077.4:c.-45G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NM_001128425.2:c.36+11C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001048171.2:c.-7+11C>T intron variant NM_001293190.2:c.36+11C>T intron variant NM_001293192.2:c.-219+11C>T intron variant NM_001350650.2:c.-278+11C>T intron variant NM_001350651.2:c.-214+11C>T intron variant NM_001407069.1:c.36+11C>T intron variant NM_001407070.1:c.-12C>T 5 prime UTR NM_001407071.1:c.-12C>T 5 prime UTR NM_001407072.1:c.-7+15C>T intron variant NM_001407073.1:c.36+11C>T intron variant NM_012222.3:c.36+11C>T intron variant NC_000001.11:g.45340208G>A NC_000001.10:g.45805880G>A NG_008189.1:g.5263C>T NG_090899.1:g.817G>A NG_090900.1:g.149G>A LRG_220:g.5263C>T LRG_220t1:c.36+11C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000001.11:45340207:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00679 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00038
The Genome Aggregation Database (gnomAD) 0.00299
Trans-Omics for Precision Medicine (TOPMed) 0.00303
Exome Aggregation Consortium (ExAC) 0.00372
1000 Genomes Project 30x 0.00625
1000 Genomes Project 0.00679
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MUTYH | - | - |
GRCh38 GRCh37 |
2644 | 2797 | |
TOE1 | - | - |
GRCh38 GRCh37 |
159 | 311 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (8) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000126892.33 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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May 3, 2016 | RCV000579941.13 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Feb 1, 2024 | RCV001097390.20 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001353844.9 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001573000.9 | |
Benign (1) |
criteria provided, single submitter
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Apr 28, 2023 | RCV003103733.11 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Feb 28, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000170423.11
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Uncertain significance
(Feb 27, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001253668.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001728679.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000306737.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(May 07, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002067709.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Benign
(May 03, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000685614.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002570182.4
First in ClinVar: Sep 17, 2022 Last updated: Aug 18, 2023 |
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Benign
(Apr 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pontocerebellar hypoplasia type 7
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159238.4
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Dec 17, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002615376.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955783.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978830.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592671.2 First in ClinVar: Oct 02, 2016 Last updated: Apr 13, 2021 |
Comment:
The MUTYH c.36+11C>T variant was identified in 7 of 276 proband chromosomes (frequency: 0.04) from individuals or families with (Shinmura 2014,Tao 2004, Zhou 2005). The … (more)
The MUTYH c.36+11C>T variant was identified in 7 of 276 proband chromosomes (frequency: 0.04) from individuals or families with (Shinmura 2014,Tao 2004, Zhou 2005). The variant was also identified in dbSNP (ID: rs2275602) as "With other allele", in ClinVar (3x as Benign by GeneDx, Colour Genomics and Prevention Genetics), Insight Colon Cancer Gene Variant Database (4x), and in UMD-LSDB (2x as unclassified variant). The variant was also identified by our laboratory in 7 individuals including 6 with a clinical indication for hereditary colon cancer testing. The variant was not identified in GeneInsight-COGR, Cosmic, or MutDB databases. The variant was identified in control databases in 914 of 275438 chromosomes (11 homozygous) at a frequency of 0.003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 23810 chromosomes (freq: 0.00008), Other in 17 of 6424 chromosomes (freq: 0.003), Latino in 3 of 34366 chromosomes (freq: 0.00009), European Non-Finnish in 133 of 125622 chromosomes (freq: 0.001), East Asian in 467 of 18808 chromosomes (freq: 0.02), Finnish in 213 of 25526 chromosomes (freq: 0.008), and South Asian in 79 of 30766 chromosomes (freq: 0.003), while the variant was not observed in the Ashkenazi Jewish population. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing; however, the c.36+11C>T variant is located in the boundary region between MUTYH exon 1 and intron 1 and many reports have suggested that gene variants in the neighborhood of the junction are often accompanied by abnormal splicing (Tao 2008). In a Japanese population-based study, a statistically significant association was demonstrated between this variant and increased CRC risk (Tao 2008). Moreover, one haplotype containing the variant c.36+11T was demonstrated to be associated with increased CRC risk (OR of 1.43, haplotype .36+11C>T, c.504+35A>G, c.934‚à Ã2A>G, and c.1014G>C, “TGAC”). The c.36+11C>T variant was found to be in complete linkage disequilibrium with two other MUTYH variants, –280G>A and c.1389G>C. These results indicate that individuals with the MUTYH – 280A/c.36+11T/c.1431C genotypes or the TGAC haplotype are susceptible to CRC (Tao 2008). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798247.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809044.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001969905.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population. | Tao H | Cancer science | 2008 | PMID: 18271935 |
Text-mined citations for rs2275602 ...
HelpRecord last updated May 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.