4-110413574-G-T

Variant names:

• chr4-110413574-G-T
• rs2087160
• ENST00000510961.1:n.72+47770G>T

Variant summary

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

The ENST00000510961.1(ENPEP):​n.72+47770G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,516 control chromosomes in the GnomAD database, including 36,628 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 0.68 (36628 hom., cov: 31)
• Consequence: ENPEP ENST00000510961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 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.72+47770G>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103040 AN: 151402 Hom.: 36628 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.680 AC: 103054 AN: 151516 Hom.: 36628 Cov.: 31 AF XY: 0.677 AC XY: 50099 AN XY: 74006

African (AFR) AF: 0.467 AC: 19222 AN: 41152

American (AMR) AF: 0.740 AC: 11285 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2504 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2631 AN: 5146

South Asian (SAS) AF: 0.600 AC: 2882 AN: 4804

European-Finnish (FIN) AF: 0.787 AC: 8225 AN: 10450

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.794 AC: 53962 AN: 67936

Other (OTH) AF: 0.704 AC: 1484 AN: 2108

Alfa AF: 0.749 Hom.: 94454

Bravo AF: 0.672

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.62
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs2087160; hg19: chr4-111334730;