rs116941637

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.23

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant deafness - onychodystrophy syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
developmental and epileptic encephalopathy 93
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
Zimmermann-Laband syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
DOORS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zimmermann-Laband syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP6V1B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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/Likely_benign. ClinVar VariationId is 770944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 48 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B2	NM_001693.4	MANE Select	c.11G>A	p.Arg4Gln	missense	Exon 1 of 14	NP_001684.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1B2	ENST00000276390.7	TSL:1 MANE Select	c.11G>A	p.Arg4Gln	missense	Exon 1 of 14	ENSP00000276390.2	P21281
ATP6V1B2	ENST00000891263.1		c.11G>A	p.Arg4Gln	missense	Exon 1 of 15	ENSP00000561322.1
ATP6V1B2	ENST00000958718.1		c.11G>A	p.Arg4Gln	missense	Exon 1 of 14	ENSP00000628777.1

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

GnomAD2 exomes

AF:

0.00446

AC:

745

AN:

166914

AF XY:

0.00462

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 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

African (AFR)

AF:

0.00153

AC:

AN:

28768

American (AMR)

AF:

0.00561

AC:

201

AN:

35850

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

23942

East Asian (EAS)

AF:

0.00

AC:

AN:

32258

South Asian (SAS)

AF:

0.00185

AC:

148

AN:

79866

European-Finnish (FIN)

AF:

0.000438

AC:

AN:

50240

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.00734

AC:

7906

AN:

1077636

Other (OTH)

AF:

0.00610

AC:

346

AN:

56748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

536

1072

1607

2143

2679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.00482

AC:

734

AN:

152296

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00216

AC:

AN:

41574

American (AMR)

AF:

0.00732

AC:

112

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00737

AC:

501

AN:

68014

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00620

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

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

PhyloP100

2.2

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

PromoterAI

-0.075

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.17

gMVP

0.72

Mutation Taster

=95/5

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over