2-70943677-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001692.4(ATP6V1B1):c.138C>T(p.Ser46Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,456 control chromosomes in the GnomAD database, including 38,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3182 hom., cov: 32)

Exomes 𝑓: 0.20 ( 35805 hom. )

Consequence

ATP6V1B1
NM_001692.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.39

Variant links:

Genes affected

ATP6V1B1 (HGNC:853): (ATPase H+ transporting V1 subunit B1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain B subunit isoforms and is found in the kidney. Mutations in this gene cause distal renal tubular acidosis associated with sensorineural deafness. [provided by RefSeq, Jul 2008]

ATP6V1B1 links:

ENSG00000258881 (HGNC:):

ENSG00000258881 links:

VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 2008]

VAX2 links:

ATP6V1B1-AS1 (HGNC:51118): (ATP6V1B1 antisense RNA 1)

ATP6V1B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-70943677-C-T is Benign according to our data. Variant chr2-70943677-C-T is described in ClinVar as [Benign]. Clinvar id is 44225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-70943677-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4 link	c.138C>T	p.Ser46Ser	synonymous_variant	Exon 2 of 14	ENST00000234396.10	NP_001683.2	P15313
ATP6V1B1-AS1	NR_110273.1 link	n.524-1244G>A		intron_variant	Intron 2 of 2
ATP6V1B1-AS1	NR_110274.1 link	n.386-1244G>A		intron_variant	Intron 1 of 1
ATP6V1B1	XM_011532907.3 link	c.-259C>T		upstream_gene_variant			XP_011531209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396.10 link	c.138C>T	p.Ser46Ser	synonymous_variant	Exon 2 of 14	1	NM_001692.4	ENSP00000234396.4		P15313
ENSG00000258881	ENST00000606025.5 link	c.476-1244G>A		intron_variant	Intron 5 of 5	5		ENSP00000475641.1		U3KQ87

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28653

AN:

151946

Hom.:

3176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.240

AC:

60156

AN:

250570

Hom.:

9047

AF XY:

0.248

AC XY:

33603

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.553

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.204

AC:

298454

AN:

1461390

Hom.:

35805

Cov.:

AF XY:

0.210

AC XY:

152781

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.189

AC:

28670

AN:

152066

Hom.:

3182

Cov.:

AF XY:

0.196

AC XY:

14557

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.177

Hom.:

2365

Bravo

AF:

0.175

Asia WGS

AF:

0.419

AC:

1459

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.180

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: 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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ser46Ser in Exon 02 of ATP6V1B1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 17.7% (1240/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2266918). -

Renal tubular acidosis with progressive nerve deafness

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: 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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

3.8

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over