ClinVar Miner

Submissions for variant NM_001297.5(CNGB1):c.413-1G>A

gnomAD frequency: 0.00010  dbSNP: rs189234741
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000504965 SCV000914732 likely pathogenic Retinitis pigmentosa 2018-10-18 criteria provided, single submitter clinical testing 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.
Invitae RCV001056559 SCV001221009 pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing 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.
Blueprint Genetics RCV001074746 SCV001240341 pathogenic Retinal dystrophy 2019-05-16 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000678544 SCV001573652 pathogenic Retinitis pigmentosa 45 2021-04-08 criteria provided, single submitter research 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.
Fulgent Genetics, Fulgent Genetics RCV000678544 SCV002815791 pathogenic Retinitis pigmentosa 45 2022-05-17 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504965 SCV000598716 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000678544 SCV000804622 pathogenic Retinitis pigmentosa 45 2016-09-01 no assertion criteria provided clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center RCV000504965 SCV001161025 pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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