rs4401760

Variant names:

• chr7-149873604-A-C
• rs4401760
• ENST00000421974.7:c.-462A>C

Variant summary

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

The NM_001367791.1(ATP6V0E2):​c.-816A>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 NM_001367791.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367791.1. 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
	ATP6V0E2	NM_001367791.1		c.-816A>C		5_prime_UTR	Exon 1 of 5	NP_001354720.1
	ATP6V0E2	NM_001367792.1		c.-995A>C		5_prime_UTR	Exon 1 of 4	NP_001354721.1
	ATP6V0E2	NM_001367793.1		c.-741A>C		5_prime_UTR	Exon 1 of 4	NP_001354722.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0E2	ENST00000421974.7	TSL:1	c.-462A>C		5_prime_UTR	Exon 1 of 3	ENSP00000411672.3	Q8NHE4-2
	ATP6V0E2	ENST00000456496.7	TSL:1	c.-462A>C		5_prime_UTR	Exon 1 of 4	ENSP00000410220.3	Q8NHE4-1
	ATP6V0E2-AS1	ENST00000461019.5	TSL:1	n.242T>G		non_coding_transcript_exon	Exon 1 of 4

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

African (AFR) AF: 0.828 AC: 3061 AN: 3696

American (AMR) AF: 0.546 AC: 1697 AN: 3110

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 2682 AN: 4704

East Asian (EAS) AF: 0.394 AC: 4232 AN: 10736

South Asian (SAS) AF: 0.362 AC: 582 AN: 1608

European-Finnish (FIN) AF: 0.544 AC: 4547 AN: 8354

Middle Eastern (MID) AF: 0.611 AC: 406 AN: 664

European-Non Finnish (NFE) AF: 0.623 AC: 46658 AN: 74946

Other (OTH) AF: 0.610 AC: 5020 AN: 8228

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

African (AFR) AF: 0.828 AC: 34383 AN: 41528

American (AMR) AF: 0.572 AC: 8750 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1943 AN: 5132

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5746 AN: 10568

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42765 AN: 67942

Other (OTH) AF: 0.644 AC: 1362 AN: 2116

Alfa AF: 0.670 Hom.: 3517

Bravo AF: 0.669

Asia WGS AF: 0.426 AC: 1478 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.71
PhyloP100		-0.70
PromoterAI		0.083	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4401760; hg19: chr7-149570693;