rs4401760

chr7-149873604-A-C

Variant summary

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

The ENST00000421974.7(ATP6V0E2):c.-462A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 268,134 control chromosomes in the GnomAD database, including 54,758 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 0.65 (33792 hom., cov: 35)
  • Exomes 𝑓: 0.59 (20966 hom.)
• Consequence: ATP6V0E2 ENST00000421974.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

Genes affected

ATP6V0E2 (HGNC:21723): (ATPase H+ transporting V0 subunit e2) Multisubunit vacuolar-type proton pumps, or H(+)-ATPases, acidify various intracellular compartments, such as vacuoles, clathrin-coated and synaptic vesicles, endosomes, lysosomes, and chromaffin granules. H(+)-ATPases are also found in plasma membranes of specialized cells, where they play roles in urinary acidification, bone resorption, and sperm maturation. Multiple subunits form H(+)-ATPases, with proteins of the V1 class hydrolyzing ATP for energy to transport H+, and proteins of the V0 class forming an integral membrane domain through which H+ is transported. ATP6V0E2 encodes an isoform of the H(+)-ATPase V0 e subunit, an essential proton pump component (Blake-Palmer et al., 2007 [PubMed 17350184]).[supplied by OMIM, Mar 2008]

ATP6V0E2-AS1 (HGNC:44180): (ATP6V0E2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0E2-AS1	NR_027040.1	n.259T>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0E2-AS1	ENST00000464939.1	n.243-1808T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99501 AN: 151978 Hom.: 33762 Cov.: 35

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.594 AC: 68885 AN: 116046 Hom.: 20966 Cov.: 2 AF XY: 0.594 AC XY: 34415 AN XY: 57930

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.655 AC: 99586 AN: 152088 Hom.: 33792 Cov.: 35 AF XY: 0.644 AC XY: 47890 AN XY: 74312

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.644

Alfa AF: 0.662 Hom.: 3260

Bravo AF: 0.669

Asia WGS AF: 0.426 AC: 1478 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.9
Dann	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4401760; hg19: chr7-149570693;