ENST00000510961.1:n.73-12749T>C

Variant names:

• chr4-110475792-T-C
• rs1879053
• ENST00000510961.1:n.73-12749T>C

Variant summary

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

The ENST00000510961.1(ENPEP):​n.73-12749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,142 control chromosomes in the GnomAD database, including 27,221 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 0.59 (27221 hom., cov: 33)
• Consequence: ENPEP ENST00000510961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 5 publications found

Genes affected

ENPEP (HGNC:3355): (glutamyl aminopeptidase) The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]

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 (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPEP	ENST00000510961.1	n.73-12749T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90410 AN: 152024 Hom.: 27197 Cov.: 33

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90481 AN: 152142 Hom.: 27221 Cov.: 33 AF XY: 0.597 AC XY: 44405 AN XY: 74382

African (AFR) AF: 0.618 AC: 25634 AN: 41500

American (AMR) AF: 0.696 AC: 10648 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3906 AN: 5174

South Asian (SAS) AF: 0.532 AC: 2566 AN: 4822

European-Finnish (FIN) AF: 0.534 AC: 5651 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38242 AN: 67988

Other (OTH) AF: 0.567 AC: 1195 AN: 2108

Alfa AF: 0.578 Hom.: 23260

Bravo AF: 0.614

Asia WGS AF: 0.650 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		-1.0
PromoterAI		0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1879053; hg19: chr4-111396948;