ClinVar Miner

Submissions for variant NM_001297.5(CNGB1):c.2794+1G>A

gnomAD frequency: 0.00009  dbSNP: rs770011113
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000487966 SCV000575055 likely pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, Institute for Ophthalmic Research RCV001199466 SCV001162475 pathogenic Retinitis pigmentosa 2020-01-09 criteria provided, single submitter research
Blueprint Genetics RCV001074635 SCV001240227 likely pathogenic Retinal dystrophy 2019-02-06 criteria provided, single submitter clinical testing
Invitae RCV000487966 SCV001408362 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 27 of the CNGB1 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 CNGB1 are known to be pathogenic (PMID: 15557452, 24043777). This variant is present in population databases (rs770011113, gnomAD 0.06%). 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: 425109). Disruption of this splice site has been observed in individuals with clinical features of retinitis pigmentosa (PMID: 33847019; Invitae).
DBGen Ocular Genomics RCV001725185 SCV001960893 pathogenic Retinitis pigmentosa 45 2021-10-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199466 SCV004242021 pathogenic Retinitis pigmentosa 2023-12-08 criteria provided, single submitter clinical testing Variant summary: CNGB1 c.2794+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. The variant allele was found at a frequency of 9.2e-05 in 249286 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CNGB1 causing Retinitis Pigmentosa (9.2e-05 vs 0.00063), allowing no conclusion about variant significance. c.2794+1G>A has been reported in the literature in individuals affected with Retinitis Pigmentosa (eg. Weisschuh_2020). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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