dbSNP rs2428953: ATP6V0B:n.1924G>A (chr1-43977787-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000468183.5(ATP6V0B):n.1924G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,508,202 control chromosomes in the GnomAD database, including 15,574 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3768 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11806 hom. )

Consequence

ATP6V0B
ENST00000468183.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

10 publications found

Variant links:

Genes affected

ATP6V0B (HGNC:861): (ATPase H+ transporting V0 subunit b) This gene encodes a portion of the V0 domain of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Activity of this enzyme is necessary for such varied processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ATP6V0B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0B	NM_004047.5 link	c.592-194G>A	intron_variant	Intron 7 of 7	ENST00000472174.7	NP_004038.1	Q99437-1
ATP6V0B	NM_001294333.2 link	c.*376G>A	3_prime_UTR_variant	Exon 7 of 7		NP_001281262.1	E9PNL3
ATP6V0B	NM_001039457.3 link	c.451-194G>A	intron_variant	Intron 6 of 6		NP_001034546.1	Q99437-2
ATP6V0B	XM_047422650.1 link	c.451-194G>A	intron_variant	Intron 6 of 6		XP_047278606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7 link	c.592-194G>A		intron_variant	Intron 7 of 7	1	NM_004047.5	ENSP00000431605.1		Q99437-1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28966

AN:

151964

Hom.:

3770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0945

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.0769

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.119

AC:

160725

AN:

1356120

Hom.:

11806

Cov.:

AF XY:

0.121

AC XY:

80185

AN XY:

664554

show subpopulations

African (AFR)

AF:

0.377

AC:

11564

AN:

30694

American (AMR)

AF:

0.214

AC:

6542

AN:

30550

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

4559

AN:

20948

East Asian (EAS)

AF:

0.0992

AC:

3765

AN:

37972

South Asian (SAS)

AF:

0.208

AC:

14731

AN:

70802

European-Finnish (FIN)

AF:

0.0792

AC:

3230

AN:

40778

Middle Eastern (MID)

AF:

0.225

AC:

1203

AN:

5350

European-Non Finnish (NFE)

AF:

0.101

AC:

107256

AN:

1062616

Other (OTH)

AF:

0.140

AC:

7875

AN:

56410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6863

13726

20589

27452

34315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4240

8480

12720

16960

21200

<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:

0.191

AC:

28994

AN:

152082

Hom.:

3768

Cov.:

AF XY:

0.191

AC XY:

14180

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.362

AC:

15018

AN:

41444

American (AMR)

AF:

0.197

AC:

3010

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

768

AN:

3470

East Asian (EAS)

AF:

0.0944

AC:

489

AN:

5182

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4822

European-Finnish (FIN)

AF:

0.0769

AC:

814

AN:

10592

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7331

AN:

67978

Other (OTH)

AF:

0.164

AC:

347

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1102

2204

3305

4407

5509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.160

Hom.:

915

Bravo

AF:

0.206

Asia WGS

AF:

0.152

AC:

530

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.15

(source)

DANN

Benign

0.61

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over