Variant 8-20197417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001693.4(ATP6V1B2):c.11G>A(p.Arg4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,542,040 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 48 hom. )

Consequence

ATP6V1B2
NM_001693.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.23

Variant links:

Genes affected

ATP6V1B2 (HGNC:854): (ATPase H+ transporting V1 subunit B2) 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, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of two V1 domain B subunit isoforms and is the only B isoform highly expressed in osteoclasts. [provided by RefSeq, Jul 2008]

ATP6V1B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009298593).

BP6

Variant 8-20197417-G-A is Benign according to our data. Variant chr8-20197417-G-A is described in ClinVar as [Benign]. Clinvar id is 770944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1B2	NM_001693.4 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/14	ENST00000276390.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1B2	ENST00000276390.7 linkuse as main transcript	c.11G>A	p.Arg4Gln	missense_variant	1/14	1	NM_001693.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

734

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00737

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00446

AC:

745

AN:

166914

Hom.:

AF XY:

0.00462

AC XY:

429

AN XY:

92816

show subpopulations

Gnomad AFR exome

AF:

0.00267

Gnomad AMR exome

AF:

0.00525

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00693

Gnomad OTH exome

AF:

0.00687

GnomAD4 exome

AF:

0.00631

AC:

8763

AN:

1389744

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

4359

AN XY:

690218

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.000438

Gnomad4 NFE exome

AF:

0.00734

Gnomad4 OTH exome

AF:

0.00610

GnomAD4 genome

AF:

0.00482

AC:

734

AN:

152296

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00737

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00566

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00251

AC:

ESP6500EA

AF:

0.00724

AC:

ExAC

AF:

0.00386

AC:

464

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ATP6V1B2: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.16

Eigen_PC

Benign

0.049

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0093

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.68

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.030

REVEL

Uncertain

0.37

Sift

Uncertain

0.013

Sift4G

Benign

0.23

Polyphen

0.0040

Vest4

0.44

MVP

0.83

MPC

0.014

ClinPred

0.061

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.17

gMVP

0.72

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

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