ClinVar Genomic variation as it relates to human health
NM_024649.5(BBS1):c.951+1G>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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024649.5(BBS1):c.951+1G>A
Variation ID: 370919 Accession: VCV000370919.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.2 11: 66523577 (GRCh38) [ NCBI UCSC ] 11: 66291048 (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 Jan 7, 2017 Feb 14, 2024 Oct 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024649.5:c.951+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001348571.2:c.*22-2111C>T intron variant NC_000011.10:g.66523577G>A NC_000011.9:g.66291048G>A NG_009093.1:g.17930G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000011.10:66523576: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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BBS1 | - | - |
GRCh38 GRCh37 |
432 | 1072 | |
ZDHHC24 | - | - | - |
GRCh38 GRCh37 |
13 | 650 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Oct 4, 2023 | RCV000410778.14 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 4, 2023 | RCV000735921.15 | |
Pathogenic (1) |
criteria provided, single submitter
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May 13, 2022 | RCV002248642.10 |
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
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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
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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
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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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Pathogenic
(Aug 17, 2020)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001431953.1
First in ClinVar: Sep 14, 2020 Last updated: Sep 14, 2020 |
Comment:
Variant summary: BBS1 c.951+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: BBS1 c.951+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251330 control chromosomes. c.951+1G>A has been reported in the literature in multiple individuals affected with features of Bardet-Biedl Syndrome (example, Fauser_2003, Redin_2012, Forsyth_2017, Komazec_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=3)/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Nov 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 1
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366246.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP4. This variant was detected in homozygous state.
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Pathogenic
(Sep 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 1
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002572580.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). It is predicted to alter splicing, resulting … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). It is predicted to alter splicing, resulting in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (3billion dataset). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000370919 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Mixed astigmatism (present) , Esophoria (present) , Night blindness (present) , Night blindness (present) , Truncal obesity (present) , Foot polydactyly (present) , Hand polydactyly … (more)
Mixed astigmatism (present) , Esophoria (present) , Night blindness (present) , Night blindness (present) , Truncal obesity (present) , Foot polydactyly (present) , Hand polydactyly (present) , Heart murmur (present) (less)
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Likely pathogenic
(May 20, 2016)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486351.2
First in ClinVar: Jan 07, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(May 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002520317.2
First in ClinVar: May 28, 2022 Last updated: Mar 04, 2023 |
Comment:
Observed with a second variant in the BBS1 gene (phase unknown) in a patient with Bardet-Biedl syndrome (Fauser et al., 2003); Canonical splice site variant … (more)
Observed with a second variant in the BBS1 gene (phase unknown) in a patient with Bardet-Biedl syndrome (Fauser et al., 2003); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30614526, 30259503, 12920096, 22773737, 27659767) (less)
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Pathogenic
(Oct 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004217362.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001577422.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370919). Disruption of this splice site has been observed in individuals with Bardet-Biedl syndrome (PMID: 12920096, 27659767, 30614526). This variant is present in population databases (rs746875134, gnomAD 0.003%). This sequence change affects a donor splice site in intron 10 of the BBS1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). (less)
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Pathogenic
(Sep 15, 2018)
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no assertion criteria provided
Method: provider interpretation
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Bardet-Biedl syndrome
Affected status: yes
Allele origin:
germline
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Study: French fetal BBS cohort
Accession: SCV000839554.1 First in ClinVar: Jan 12, 2019 Last updated: Jan 12, 2019 |
Age: 20-29 weeks gestation
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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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Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes. | Mary L | Clinical genetics | 2019 | PMID: 30614526 |
The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young. | Komazec J | Endokrynologia Polska | 2019 | PMID: 30259503 |
Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome. | Forsythe E | Journal of the American Society of Nephrology : JASN | 2017 | PMID: 27659767 |
Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel. | Bravo-Gil N | Scientific reports | 2016 | PMID: 27032803 |
Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alström syndromes. | Redin C | Journal of medical genetics | 2012 | PMID: 22773737 |
U1 snRNA-mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation. | Schmid F | Human mutation | 2011 | PMID: 21520335 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Further support for digenic inheritance in Bardet-Biedl syndrome. | Fauser S | Journal of medical genetics | 2003 | PMID: 12920096 |
Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. | Mykytyn K | Nature genetics | 2002 | PMID: 12118255 |
Text-mined citations for rs746875134 ...
HelpRecord last updated Jun 02, 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.