ClinVar Miner

Submissions for variant NM_000744.6(CHRNA4):c.1376G>A (p.Gly459Glu) (rs753201154)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486682 SCV000570493 uncertain significance not specified 2016-06-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHRNA4 gene. The G459E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G459E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. Additionally, this amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000539550 SCV000658068 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2017-08-18 criteria provided, single submitter clinical testing

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