dbSNP rs3756249: ENPEP:n.73-12482A>G (chr4-110476059-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000510961.1(ENPEP):n.73-12482A>G variant causes a intron change. The variant allele was found at a frequency of 0.00786 in 180,254 control chromosomes in the GnomAD database, including 44 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 0.0082 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 5 hom. )

Consequence

ENPEP
ENST00000510961.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Publications

4 publications found

Variant links:

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]

ENPEP links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000510961.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510961.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENPEP	NM_001977.4	MANE Select	c.-356A>G	upstream_gene	N/A	NP_001968.3
ENPEP	NM_001379611.1		c.-356A>G	upstream_gene	N/A	NP_001366540.1
ENPEP	NM_001379612.1		c.-356A>G	upstream_gene	N/A	NP_001366541.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENPEP	ENST00000510961.1	TSL:5	n.73-12482A>G	intron	N/A
ENPEP	ENST00000265162.10	TSL:1 MANE Select	c.-356A>G	upstream_gene	N/A	ENSP00000265162.5	Q07075
ENPEP	ENST00000876172.1		c.-356A>G	upstream_gene	N/A	ENSP00000546231.1

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.00589

AC:

165

AN:

28010

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

AN XY:

14316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1028

American (AMR)

AF:

0.00

AC:

AN:

3014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

854

East Asian (EAS)

AF:

0.0548

AC:

AN:

1806

South Asian (SAS)

AF:

0.000617

AC:

AN:

1622

European-Finnish (FIN)

AF:

0.0545

AC:

AN:

918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

17014

Other (OTH)

AF:

0.00421

AC:

AN:

1664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00822

AC:

1252

AN:

152244

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

871

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.000261

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0659

AC:

340

AN:

5156

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0763

AC:

808

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00119

AC:

AN:

68026

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

4.6

PromoterAI

0.023

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over