4-110475792-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000510961.1(ENPEP):n.73-12749T>C 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 0.595 in 152,142 control chromosomes in the GnomAD database, including 27,221 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 0.59 (27221 hom., cov: 33)
• Consequence: ENPEP ENST00000510961.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 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.73-12749T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90410 AN: 152024 Hom.: 27197 Cov.: 33

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.595 AC: 90481 AN: 152142 Hom.: 27221 Cov.: 33 AF XY: 0.597 AC XY: 44405 AN XY: 74382

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.567

Alfa AF: 0.578 Hom.: 17344

Bravo AF: 0.614

Asia WGS AF: 0.650 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1879053; hg19: chr4-111396948;