4-110413574-G-T

Position:

• chr4-110413574-G-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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPEP	ENST00000510961.1	n.72+47770G>T		intron_variant, non_coding_transcript_variant		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;