ClinVar Miner

Submissions for variant NM_033028.5(BBS4):c.65G>A (p.Arg22Gln)

gnomAD frequency: 0.00001  dbSNP: rs775955872
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001316446 SCV001507065 uncertain significance Bardet-Biedl syndrome 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 22 of the BBS4 protein (p.Arg22Gln). 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 not been reported in the literature in individuals affected with BBS4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1017314). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002504488 SCV002815781 uncertain significance Bardet-Biedl syndrome 4 2024-04-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003399095 SCV004105805 uncertain significance BBS4-related disorder 2024-05-22 no assertion criteria provided clinical testing The BBS4 c.65G>A variant is predicted to result in the amino acid substitution p.Arg22Gln. This variant was reported as uncertain in one individual with Bardet Biedl syndrome, who also carried two truncating variants in BBS12 gene (Tables S1 and S3, Nasser et al. 2022. PubMed ID: 35886001). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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