Submissions for variant NM_001985.3(ETFB):c.292C>T (p.Arg98Cys)

gnomAD frequency: 0.00133  dbSNP: rs147353781

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185874	SCV000238826	benign	not specified	2014-07-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Center for Human Genetics Tuebingen	RCV000658852	SCV000780649	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	ETFB: PM2, BP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086047	SCV001013135	likely benign	Multiple acyl-CoA dehydrogenase deficiency	2024-01-26	criteria provided, single submitter	clinical testing
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV001171332	SCV001328279	uncertain significance	Chronic kidney disease	2020-05-28	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000185874	SCV004813892	likely benign	not specified	2024-02-08	criteria provided, single submitter	clinical testing	Variant summary: ETFB c.292C>T (p.Arg98Cys) results in a non-conservative amino acid change located in the Electron transfer flavoprotein, alpha/beta-subunit, N-terminal (IPR014730) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 251232 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 1 fold of the estimated maximal expected allele frequency for a pathogenic variant in ETFB causing Glutaric Aciduria, Type 2b phenotype (0.0011), strongly suggesting that the variant is benign. c.292C>T has been reported in the literature in an individual affected with mitochondrial disorders (DaRe_2013), without strong evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Glutaric Aciduria, Type 2b. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24215330). ClinVar contains an entry for this variant (Variation ID: 203697). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003907648	SCV004719220	likely benign	ETFB-related disorder	2020-01-08	no assertion criteria provided	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).