chr1-43977787-G-A

Variant names:

• chr1-43977787-G-A
• rs2428953
• NM_004047.5:c.592-194G>A

Variant summary

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

The NM_001294333.2(ATP6V0B):​c.*376G>A variant causes a 3 prime UTR 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_001294333.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294333.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0B	NM_004047.5	MANE Select	c.592-194G>A		intron	N/A	NP_004038.1	Q99437-1
	ATP6V0B	NM_001294333.2		c.*376G>A		3_prime_UTR	Exon 7 of 7	NP_001281262.1	E9PNL3
	ATP6V0B	NM_001039457.3		c.451-194G>A		intron	N/A	NP_001034546.1	Q99437-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0B	ENST00000472174.7	TSL:1 MANE Select	c.592-194G>A		intron	N/A	ENSP00000431605.1	Q99437-1
	ATP6V0B	ENST00000468183.5	TSL:1	n.1924G>A		non_coding_transcript_exon	Exon 6 of 6
	ATP6V0B	ENST00000532642.5	TSL:2	c.*376G>A		3_prime_UTR	Exon 7 of 7	ENSP00000434729.1	E9PNL3

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

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

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

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: 45 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7331 AN: 67978

Other (OTH) AF: 0.164 AC: 347 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
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)

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