rs3756249

chr4-110476059-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000510961.1(ENPEP):n.73-12482A>G variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPEP	ENST00000510961.1	n.73-12482A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0548

Gnomad4 SAS exome AF: 0.000617

Gnomad4 FIN exome AF: 0.0545

Gnomad4 NFE exome AF: 0.000470

Gnomad4 OTH exome AF: 0.00421

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.00568

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	17
Dann	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756249; hg19: chr4-111397215;