rs17853498

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001692.4(ATP6V1B1):c.27T>C(p.Pro9Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,628 control chromosomes in the GnomAD database, including 10,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1258 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8939 hom. )

Consequence

ATP6V1B1
NM_001692.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.64

Publications

12 publications found

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:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-70935981-T-C is Benign according to our data. Variant chr2-70935981-T-C is described in ClinVar as Benign. ClinVar VariationId is 44227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4 link	c.27T>C	p.Pro9Pro	synonymous_variant	Exon 1 of 14	ENST00000234396.10	NP_001683.2	P15313

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396.10 link	c.27T>C	p.Pro9Pro	synonymous_variant	Exon 1 of 14	1	NM_001692.4	ENSP00000234396.4		P15313

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18017

AN:

151990

Hom.:

1256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.118

AC:

29531

AN:

250604

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0569

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0879

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.102

AC:

149113

AN:

1461520

Hom.:

8939

Cov.:

AF XY:

0.105

AC XY:

76297

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.166

AC:

5541

AN:

33470

American (AMR)

AF:

0.0587

AC:

2624

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3117

AN:

26118

East Asian (EAS)

AF:

0.198

AC:

7860

AN:

39696

South Asian (SAS)

AF:

0.201

AC:

17361

AN:

86238

European-Finnish (FIN)

AF:

0.106

AC:

5651

AN:

53340

Middle Eastern (MID)

AF:

0.122

AC:

705

AN:

5762

European-Non Finnish (NFE)

AF:

0.0892

AC:

99178

AN:

1111834

Other (OTH)

AF:

0.117

AC:

7076

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6850

13700

20550

27400

34250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3852

7704

11556

15408

19260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.119

AC:

18030

AN:

152108

Hom.:

1258

Cov.:

AF XY:

0.122

AC XY:

9096

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.160

AC:

6633

AN:

41480

American (AMR)

AF:

0.0780

AC:

1193

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

412

AN:

3468

East Asian (EAS)

AF:

0.225

AC:

1160

AN:

5154

South Asian (SAS)

AF:

0.199

AC:

957

AN:

4810

European-Finnish (FIN)

AF:

0.109

AC:

1151

AN:

10608

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0904

AC:

6146

AN:

67980

Other (OTH)

AF:

0.112

AC:

236

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

800

1600

2400

3200

4000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0800

Hom.:

282

Bravo

AF:

0.114

Asia WGS

AF:

0.182

AC:

633

AN:

3478

EpiCase

AF:

0.0921

EpiControl

AF:

0.0899

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro9Pro in Exon 01 of ATP6V1B1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 15.4% (577/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17853498). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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. -

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.64

PhyloP100

-2.6

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over