rs3756249

Variant names:

• chr4-110476059-A-G
• rs3756249
• ENST00000510961.1:n.73-12482A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000510961.1(ENPEP):​n.73-12482A>G variant causes a intron change. The variant allele was found at a frequency of 0.00786 in 180,254 control chromosomes in the GnomAD database, including 44 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 0.0082 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (5 hom.)
• Consequence: ENPEP ENST00000510961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510961.1. 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
	ENPEP	NM_001977.4	MANE Select	c.-356A>G		upstream_gene	N/A	NP_001968.3
	ENPEP	NM_001379611.1		c.-356A>G		upstream_gene	N/A	NP_001366540.1
	ENPEP	NM_001379612.1		c.-356A>G		upstream_gene	N/A	NP_001366541.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPEP	ENST00000510961.1	TSL:5	n.73-12482A>G		intron	N/A
	ENPEP	ENST00000265162.10	TSL:1 MANE Select	c.-356A>G		upstream_gene	N/A	ENSP00000265162.5
	ENPEP	ENST00000876172.1		c.-356A>G		upstream_gene	N/A	ENSP00000546231.1

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1252 AN: 152126 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00589 AC: 165 AN: 28010 Hom.: 5 Cov.: 0 AF XY: 0.00580 AC XY: 83 AN XY: 14316

African (AFR) AF: 0.00 AC: 0 AN: 1028

American (AMR) AF: 0.00 AC: 0 AN: 3014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 854

East Asian (EAS) AF: 0.0548 AC: 99 AN: 1806

South Asian (SAS) AF: 0.000617 AC: 1 AN: 1622

European-Finnish (FIN) AF: 0.0545 AC: 50 AN: 918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 90

European-Non Finnish (NFE) AF: 0.000470 AC: 8 AN: 17014

Other (OTH) AF: 0.00421 AC: 7 AN: 1664

GnomAD4 genome AF: 0.00822 AC: 1252 AN: 152244 Hom.: 39 Cov.: 32 AF XY: 0.0117 AC XY: 871 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0659 AC: 340 AN: 5156

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.0763 AC: 808 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00365 Hom.: 1

Bravo AF: 0.00272

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		4.6
PromoterAI		0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3756249; hg19: chr4-111397215;