dbSNP rs2266918: ATP6V1B1:p.Ser46Ser (chr2-70943677-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -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:9

Conservation

PhyloP100: -2.39

Publications

18 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:

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

ATP6V1B1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001692.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP6V1B1	NM_001692.4	MANE Select	c.138C>T	p.Ser46Ser	synonymous	Exon 2 of 14	NP_001683.2
ATP6V1B1-AS1	NR_110273.1		n.524-1244G>A		intron	N/A
ATP6V1B1-AS1	NR_110274.1		n.386-1244G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.138C>T	p.Ser46Ser	synonymous	Exon 2 of 14	ENSP00000234396.4	P15313
ENSG00000258881	ENST00000606025.5	TSL:5	c.476-1244G>A		intron	N/A	ENSP00000475641.1	U3KQ87
ATP6V1B1	ENST00000872157.1		c.138C>T	p.Ser46Ser	synonymous	Exon 2 of 14	ENSP00000542216.1

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

GnomAD2 exomes

AF:

0.240

AC:

60156

AN:

250570

AF XY:

0.248

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 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

African (AFR)

AF:

0.118

AC:

3940

AN:

33472

American (AMR)

AF:

0.196

AC:

8778

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5798

AN:

26132

East Asian (EAS)

AF:

0.540

AC:

21434

AN:

39698

South Asian (SAS)

AF:

0.395

AC:

34047

AN:

86240

European-Finnish (FIN)

AF:

0.243

AC:

12944

AN:

53196

Middle Eastern (MID)

AF:

0.288

AC:

1654

AN:

5744

European-Non Finnish (NFE)

AF:

0.177

AC:

196591

AN:

1111834

Other (OTH)

AF:

0.220

AC:

13268

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

13389

26778

40167

53556

66945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7164

14328

21492

28656

35820

<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:

0.189

AC:

28670

AN:

152066

Hom.:

3182

Cov.:

AF XY:

0.196

AC XY:

14557

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.119

AC:

4918

AN:

41490

American (AMR)

AF:

0.177

AC:

2709

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

783

AN:

3470

East Asian (EAS)

AF:

0.525

AC:

2691

AN:

5130

South Asian (SAS)

AF:

0.397

AC:

1914

AN:

4826

European-Finnish (FIN)

AF:

0.234

AC:

2480

AN:

10612

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12542

AN:

67944

Other (OTH)

AF:

0.186

AC:

393

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1185

2370

3554

4739

5924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.173

Hom.:

3001

Bravo

AF:

0.175

Asia WGS

AF:

0.419

AC:

1459

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.180

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

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

-0.36

CADD

Benign

3.8

(source)

DANN

Benign

0.84

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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