4-110413574-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.704

Alfa AF: 0.762 Hom.: 16423

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2087160; hg19: chr4-111334730;