rs2072462

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.1002C>T(p.Arg334Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,613,544 control chromosomes in the GnomAD database, including 172,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12924 hom., cov: 32)

Exomes 𝑓: 0.46 ( 159081 hom. )

Consequence

ATP6V1B1
NM_001692.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.74

Publications

21 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:

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:

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=-0.55).

BP6

Variant 2-70963254-C-T is Benign according to our data. Variant chr2-70963254-C-T is described in ClinVar as Benign. ClinVar VariationId is 44222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001692.4. 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
	ATP6V1B1	NM_001692.4	MANE Select	c.1002C>T	p.Arg334Arg	synonymous	Exon 10 of 14	NP_001683.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.1002C>T	p.Arg334Arg	synonymous	Exon 10 of 14	ENSP00000234396.4	P15313
ENSG00000258881	ENST00000606025.5	TSL:5	c.476-20821G>A		intron	N/A	ENSP00000475641.1	U3KQ87
ATP6V1B1	ENST00000872157.1		c.1002C>T	p.Arg334Arg	synonymous	Exon 10 of 14	ENSP00000542216.1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58766

AN:

151886

Hom.:

12924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.392

GnomAD2 exomes

AF:

0.477

AC:

119788

AN:

251080

AF XY:

0.483

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.512

Gnomad EAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.461

AC:

673324

AN:

1461540

Hom.:

159081

Cov.:

AF XY:

0.464

AC XY:

337564

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.168

AC:

5614

AN:

33480

American (AMR)

AF:

0.549

AC:

24532

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13298

AN:

26134

East Asian (EAS)

AF:

0.661

AC:

26232

AN:

39700

South Asian (SAS)

AF:

0.586

AC:

50567

AN:

86256

European-Finnish (FIN)

AF:

0.402

AC:

21340

AN:

53112

Middle Eastern (MID)

AF:

0.523

AC:

3018

AN:

5768

European-Non Finnish (NFE)

AF:

0.451

AC:

501100

AN:

1111972

Other (OTH)

AF:

0.457

AC:

27623

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

25649

51297

76946

102594

128243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15208

30416

45624

60832

76040

<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:

0.387

AC:

58775

AN:

152004

Hom.:

12924

Cov.:

AF XY:

0.389

AC XY:

28910

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.176

AC:

7303

AN:

41504

American (AMR)

AF:

0.470

AC:

7179

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1805

AN:

3462

East Asian (EAS)

AF:

0.656

AC:

3377

AN:

5146

South Asian (SAS)

AF:

0.575

AC:

2765

AN:

4808

European-Finnish (FIN)

AF:

0.396

AC:

4196

AN:

10588

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30743

AN:

67910

Other (OTH)

AF:

0.393

AC:

827

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1634

3269

4903

6538

8172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.428

Hom.:

40214

Bravo

AF:

0.383

Asia WGS

AF:

0.563

AC:

1956

AN:

3478

EpiCase

AF:

0.457

EpiControl

AF:

0.460

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Renal tubular acidosis with progressive nerve deafness (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.5

(source)

DANN

Benign

0.92

PhyloP100

-3.7

PromoterAI

0.038

Neutral

(source)

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over