rs2428953

chr1-43977787-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004047.5(ATP6V0B):c.592-194G>A variant causes a intron 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 NM_004047.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0B	NM_004047.5	c.592-194G>A		intron_variant		ENST00000472174.7
ATP6V0B	NM_001294333.2	c.*376G>A		3_prime_UTR_variant	7/7
ATP6V0B	NM_001039457.3	c.451-194G>A		intron_variant
ATP6V0B	XM_047422650.1	c.451-194G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.592-194G>A		intron_variant		1	NM_004047.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28966 AN: 151964 Hom.: 3770 Cov.: 32

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.: 32 AF XY: 0.121 AC XY: 80185 AN XY: 664554

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.0992

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.0792

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.191 AC: 28994 AN: 152082 Hom.: 3768 Cov.: 32 AF XY: 0.191 AC XY: 14180 AN XY: 74372

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.164

Alfa AF: 0.160 Hom.: 456

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
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2428953; hg19: chr1-44443459; COSMIC: COSV52543413; COSMIC: COSV52543413;