Submissions for variant NM_000101.4(CYBA):c.403G>A (p.Glu135Lys)

gnomAD frequency: 0.00300  dbSNP: rs114610092

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000294954	SCV000343863	likely benign	not specified	2016-07-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000766493	SCV000589448	uncertain significance	not provided	2016-06-28	criteria provided, single submitter	clinical testing	The E135K variant has been published previously as as a benign variant (Rae et al., 2000). The NHLBI Exome Sequencing Project reports the variant was observed in 9/2910 (0.31%) alleles from individuals of African-American background, and the 1000 Genomes Project Consortium reports E135K was observed in 18/1322 (1.36%) alleles from individuals of African background, indicating it may be a rare variant in these populations. However, the 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. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is 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	RCV001080551	SCV000763957	benign	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	2024-01-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003920153	SCV004736865	likely benign	CYBA-related condition	2020-03-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).