chr1-43976849-A-C

Variant names:

• chr1-43976849-A-C
• rs12410334
• NM_004047.5:c.400+25A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004047.5(ATP6V0B):​c.400+25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,613,184 control chromosomes in the GnomAD database, including 500,080 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 0.63 (35274 hom., cov: 33)
  • Exomes 𝑓: 0.79 (464806 hom.)
• Consequence: ATP6V0B NM_004047.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 20 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0B	NM_004047.5	c.400+25A>C		intron_variant	Intron 6 of 7	ENST00000472174.7	NP_004038.1
ATP6V0B	NM_001294333.2	c.400+25A>C		intron_variant	Intron 6 of 6		NP_001281262.1
ATP6V0B	NM_001039457.3	c.259+25A>C		intron_variant	Intron 5 of 6		NP_001034546.1
ATP6V0B	XM_047422650.1	c.259+25A>C		intron_variant	Intron 5 of 6		XP_047278606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.400+25A>C		intron_variant	Intron 6 of 7	1	NM_004047.5	ENSP00000431605.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95219 AN: 152044 Hom.: 35269 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.677

GnomAD2 exomes AF: 0.722 AC: 181424 AN: 251202 AF XY: 0.735

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.704

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.805

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.790 AC: 1153494 AN: 1461022 Hom.: 464806 Cov.: 54 AF XY: 0.789 AC XY: 573308 AN XY: 726870

African (AFR) AF: 0.179 AC: 5994 AN: 33470

American (AMR) AF: 0.625 AC: 27942 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 18479 AN: 26132

East Asian (EAS) AF: 0.701 AC: 27842 AN: 39694

South Asian (SAS) AF: 0.691 AC: 59622 AN: 86228

European-Finnish (FIN) AF: 0.807 AC: 43094 AN: 53410

Middle Eastern (MID) AF: 0.638 AC: 3623 AN: 5678

European-Non Finnish (NFE) AF: 0.829 AC: 921644 AN: 1111346

Other (OTH) AF: 0.750 AC: 45254 AN: 60354

GnomAD4 genome AF: 0.626 AC: 95246 AN: 152162 Hom.: 35274 Cov.: 33 AF XY: 0.626 AC XY: 46573 AN XY: 74382

African (AFR) AF: 0.208 AC: 8646 AN: 41496

American (AMR) AF: 0.663 AC: 10133 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3841 AN: 5182

South Asian (SAS) AF: 0.683 AC: 3291 AN: 4818

European-Finnish (FIN) AF: 0.798 AC: 8464 AN: 10602

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55992 AN: 67994

Other (OTH) AF: 0.680 AC: 1435 AN: 2110

Alfa AF: 0.739 Hom.: 61289

Bravo AF: 0.599

Asia WGS AF: 0.703 AC: 2446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12410334; hg19: chr1-44442521;