Genetic Variant ATP6V0B:p.Ala19Ala (chr1-43975097-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004047.5(ATP6V0B):c.57G>C(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 1,407,126 control chromosomes in the GnomAD database, including 2,569 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 0.058 ( 283 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2286 hom. )

Consequence

ATP6V0B
NM_004047.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

15 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:

LOC124904167 (HGNC:):

LOC124904167 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP7

Synonymous conserved (PhyloP=0.515 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0B	NM_004047.5 link	c.57G>C	p.Ala19Ala	synonymous_variant	Exon 1 of 8	ENST00000472174.7	NP_004038.1	Q99437-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7 link	c.57G>C	p.Ala19Ala	synonymous_variant	Exon 1 of 8	1	NM_004047.5	ENSP00000431605.1		Q99437-1

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8886

AN:

152180

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0680

Gnomad ASJ

AF:

0.0479

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0778

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.0707

GnomAD2 exomes

AF:

0.0580

AC:

1524

AN:

26288

AF XY:

0.0582

show subpopulations

Gnomad AFR exome

AF:

0.0646

Gnomad AMR exome

AF:

0.0630

Gnomad ASJ exome

AF:

0.0320

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0485

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0561

AC:

70337

AN:

1254828

Hom.:

2286

Cov.:

AF XY:

0.0562

AC XY:

34288

AN XY:

610496

show subpopulations

African (AFR)

AF:

0.0526

AC:

1274

AN:

24206

American (AMR)

AF:

0.0637

AC:

946

AN:

14852

Ashkenazi Jewish (ASJ)

AF:

0.0469

AC:

831

AN:

17736

East Asian (EAS)

AF:

0.162

AC:

4607

AN:

28480

South Asian (SAS)

AF:

0.0733

AC:

4396

AN:

59946

European-Finnish (FIN)

AF:

0.0290

AC:

1002

AN:

34606

Middle Eastern (MID)

AF:

0.0494

AC:

243

AN:

4922

European-Non Finnish (NFE)

AF:

0.0528

AC:

53790

AN:

1018350

Other (OTH)

AF:

0.0628

AC:

3248

AN:

51730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3699

7397

11096

14794

18493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2222

4444

6666

8888

11110

<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:

0.0584

AC:

8900

AN:

152298

Hom.:

283

Cov.:

AF XY:

0.0593

AC XY:

4419

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0561

AC:

2333

AN:

41576

American (AMR)

AF:

0.0683

AC:

1045

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0479

AC:

166

AN:

3466

East Asian (EAS)

AF:

0.167

AC:

865

AN:

5172

South Asian (SAS)

AF:

0.0780

AC:

377

AN:

4832

European-Finnish (FIN)

AF:

0.0290

AC:

308

AN:

10620

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0531

AC:

3612

AN:

68008

Other (OTH)

AF:

0.0737

AC:

156

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

453

906

1358

1811

2264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0535

Hom.:

Bravo

AF:

0.0605

Asia WGS

AF:

0.123

AC:

428

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.52

PromoterAI

-0.047

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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