ClinVar Miner

Submissions for variant NM_001297.5(CNGB1):c.217+5G>C

gnomAD frequency: 0.00002  dbSNP: rs527236060
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001207756 SCV001379122 pathogenic not provided 2022-10-12 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the CNGB1 gene. It does not directly change the encoded amino acid sequence of the CNGB1 protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individuals with retinitis pigmentosa (PMID: 25324289; Invitae). ClinVar contains an entry for this variant (Variation ID: 143124). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
3billion RCV002250572 SCV002521880 pathogenic Retinitis pigmentosa 45 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.005%). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.90). The variant has been observed in multiple (>3) similarly affected unrelated individuals (3billion dataset, ClinVar ID: VCV000143124). 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 (PMID: 33847019, 33946315). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV002250572 SCV002797076 likely pathogenic Retinitis pigmentosa 45 2022-03-03 criteria provided, single submitter clinical testing
GeneDx RCV001207756 SCV003935447 likely pathogenic not provided 2022-12-21 criteria provided, single submitter clinical testing Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Identified in individuals in the published literature with childhood onset night blindness who also harbored a second variant in CNGB1, although the phase of these variants was not confirmed (Nassisi et al., 2021); This variant is associated with the following publications: (PMID: 31054281, 33946315, 33847019, 25324289)
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132646 SCV000172597 probable-pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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