rs2286241

chr1-43975097-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004047.5(ATP6V0B):c.57G>C(p.Ala19=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ATP6V0B	NM_004047.5	c.57G>C	p.Ala19=	synonymous_variant	1/8	ENST00000472174.7
ATP6V0B	NM_001294333.2	c.57G>C	p.Ala19=	synonymous_variant	1/7
ATP6V0B	NM_001039457.3	c.-36G>C		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.57G>C	p.Ala19=	synonymous_variant	1/8	1	NM_004047.5	P1

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8886 AN: 152180 Hom.: 282 Cov.: 33

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

GnomAD3 exomes AF: 0.0580 AC: 1524 AN: 26288 Hom.: 69 AF XY: 0.0582 AC XY: 793 AN XY: 13616

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 SAS exome AF: 0.0661

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.: 31 AF XY: 0.0562 AC XY: 34288 AN XY: 610496

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.0637

Gnomad4 ASJ exome AF: 0.0469

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0528

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.0584 AC: 8900 AN: 152298 Hom.: 283 Cov.: 33 AF XY: 0.0593 AC XY: 4419 AN XY: 74472

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0780

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0535 Hom.: 32

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	14
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs2286241; hg19: chr1-44440769; COSMIC: COSV52542892; COSMIC: COSV52542892;