ClinVar Genomic variation as it relates to human health
NM_001297.5(CNGB1):c.413-1G>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
-
NM_001297.5(CNGB1):c.413-1G>A
Variation ID: 437976 Accession: VCV000437976.14
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16q21 16: 57962611 (GRCh38) [ NCBI UCSC ] 16: 57996515 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 9, 2017 Feb 14, 2024 Jan 8, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001297.5:c.413-1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001135639.2:c.413-1G>A splice acceptor NM_001286130.2:c.413-1G>A splice acceptor NC_000016.10:g.57962611C>T NC_000016.9:g.57996515C>T NG_016351.1:g.13506G>A - Protein change
- Other names
- -
- Canonical SPDI
- NC_000016.10:57962610:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00010
1000 Genomes Project 30x 0.00016
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00016
1000 Genomes Project 0.00020
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 | ||
---|---|---|---|---|---|---|
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. |
|||
CNGB1 | - | - |
GRCh38 GRCh37 |
1248 | 1275 |
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. |
---|---|---|---|---|
Likely pathogenic (3) |
criteria provided, single submitter
|
Oct 18, 2018 | RCV000504965.6 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
May 17, 2022 | RCV000678544.4 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 8, 2024 | RCV001056559.5 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 16, 2019 | RCV001074746.2 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Oct 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914732.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The CNGB1 c.413-1G>A variant has been reported in three studies in at least four probands with retinitis pigmentosa, all in a homozygous state (Azam et … (more)
The CNGB1 c.413-1G>A variant has been reported in three studies in at least four probands with retinitis pigmentosa, all in a homozygous state (Azam et al. 2011; Saqib et al. 2015; van Huet et al. 2015). Two of these probands were siblings and their unaffected parents were shown to carry the variant in a heterozygous state. Control data are not available for this variant which is reported at a frequency of 0.00024 in the South Asian population from the Exome Aggregation Consortium. When this variant was incorporated into a vector which was transfected into HeLa cells and retrotranscribed, the cDNA demonstrated a frameshift and introduction of a premature stop codon (Saqib et al. 2015). Based on the evidence and due to the potential impact of splice acceptor variants, the c.413-1G>A variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Pathogenic
(May 16, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001240341.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
Pathogenic
(Apr 08, 2021)
|
criteria provided, single submitter
Method: research
|
Retinitis pigmentosa 45
Affected status: yes
Allele origin:
germline
|
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573652.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The CNGB1 c.413-1G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The CNGB1 c.413-1G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PP1-M, PM3, PM2. Based on this evidence we have classified this variant as Pathogenic. (less)
|
|
Pathogenic
(May 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 45
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002815791.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Jan 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001221009.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 6 of the CNGB1 gene. RNA analysis indicates that disruption of this splice site induces … (more)
This sequence change affects an acceptor splice site in intron 6 of the CNGB1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs189234741, gnomAD 0.03%). Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 25943428). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS6-1G>A. ClinVar contains an entry for this variant (Variation ID: 437976). Studies have shown that disruption of this splice site results in activation of a cryptic splice acceptor and introduces a premature termination codon (PMID: 25943428). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jan 01, 2015)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598716.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
|
|
Pathogenic
(Sep 01, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 45
Affected status: yes
Allele origin:
unknown
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804622.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Jun 23, 2019)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
inherited
|
Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001161025.1
First in ClinVar: Feb 17, 2020 Last updated: Feb 17, 2020 |
|
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 |
---|---|---|---|---|
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. | Carss KJ | American journal of human genetics | 2017 | PMID: 28041643 |
The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice. | van Huet RA | Molecular vision | 2015 | PMID: 25999674 |
Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies. | Saqib MA | Scientific reports | 2015 | PMID: 25943428 |
Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. | Nishiguchi KM | Proceedings of the National Academy of Sciences of the United States of America | 2013 | PMID: 24043777 |
Identification of novel mutations in Pakistani families with autosomal recessive retinitis pigmentosa. | Azam M | Archives of ophthalmology (Chicago, Ill. : 1960) | 2011 | PMID: 21987686 |
Text-mined citations for rs189234741 ...
HelpRecord last updated May 08, 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.