ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.212C>T (p.Ala71Val)

gnomAD frequency: 0.00001  dbSNP: rs753677594
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498928 SCV000590756 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA4 gene. The A71V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A71V variant is observed in 1/65,436 (0.002%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A71V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001053897 SCV001218181 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2022-07-12 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 432974). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This variant is present in population databases (rs753677594, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 71 of the CHRNA4 protein (p.Ala71Val).

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