Submissions for variant NM_001692.4(ATP6V1B1):c.481G>A (p.Glu161Lys)

gnomAD frequency: 0.02502  dbSNP: rs114234874

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037208	SCV000060865	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	Glu161Lys in Exon 06 of ATP6V1B1: This variant is not expected to have clinical significance because it has been identified in 2.4% (90/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs114234874).
Eurofins Ntd Llc (ga)	RCV000037208	SCV000231627	benign	not specified	2015-01-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000299123	SCV000431634	benign	Renal tubular acidosis with progressive nerve deafness	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000037208	SCV000730650	benign	not specified	2017-11-06	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.
Counsyl	RCV000299123	SCV000790101	benign	Renal tubular acidosis with progressive nerve deafness	2017-03-06	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000991559	SCV001143091	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
Invitae	RCV000991559	SCV001717812	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000299123	SCV001761695	benign	Renal tubular acidosis with progressive nerve deafness	2021-07-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037208	SCV002050928	benign	not specified	2023-03-15	criteria provided, single submitter	clinical testing	Variant summary: ATP6V1B1 c.481G>A (p.Glu161Lys) results in a conservative amino acid change in 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 0.03 in 251352 control chromosomes in the gnomAD database, including 191 homozygotes. The observed variant frequency is approximately 27-fold of the estimated maximal expected allele frequency for a pathogenic variant in ATP6V1B1 causing Renal Tubular Acidosis With Progressive Nerve Deafness phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no penetrant association of c.481G>A with Renal Tubular Acidosis With Progressive Nerve Deafness has been reported. Nine submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. The majority classified the variant as benign (n=8), and one classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV000299123	SCV001452519	benign	Renal tubular acidosis with progressive nerve deafness	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000037208	SCV001930606	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000991559	SCV001959160	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Cyto-molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi	RCV000299123	SCV002102803	likely pathogenic	Renal tubular acidosis with progressive nerve deafness	2022-03-07	flagged submission	clinical testing