rs6825911

Variant names:

• chr4-110460482-C-T
• rs6825911
• ENST00000510961.1:n.73-28059C>T

Variant summary

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

The ENST00000510961.1(ENPEP):​n.73-28059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,008 control chromosomes in the GnomAD database, including 36,391 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 (36391 hom., cov: 30)
• Consequence: ENPEP ENST00000510961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 35 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 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.73-28059C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102828 AN: 151890 Hom.: 36390 Cov.: 30

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.677 AC: 102837 AN: 152008 Hom.: 36391 Cov.: 30 AF XY: 0.674 AC XY: 50037 AN XY: 74260

African (AFR) AF: 0.465 AC: 19263 AN: 41436

American (AMR) AF: 0.733 AC: 11192 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2619 AN: 5150

South Asian (SAS) AF: 0.602 AC: 2895 AN: 4810

European-Finnish (FIN) AF: 0.787 AC: 8324 AN: 10574

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53708 AN: 67982

Other (OTH) AF: 0.698 AC: 1475 AN: 2114

Alfa AF: 0.746 Hom.: 128118

Bravo AF: 0.669

Asia WGS AF: 0.536 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.51
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs6825911; hg19: chr4-111381638;