Variant 4-110476508-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001977.4(ENPEP):c.94A>G(p.Ile32Val) variant causes a missense change. The variant allele was found at a frequency of 0.00513 in 1,598,144 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 191 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 181 hom. )

Consequence

ENPEP
NM_001977.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.94

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014923513).

BP6

Variant 4-110476508-A-G is Benign according to our data. Variant chr4-110476508-A-G is described in ClinVar as [Benign]. Clinvar id is 780490.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPEP	NM_001977.4 linkuse as main transcript	c.94A>G	p.Ile32Val	missense_variant	1/20	ENST00000265162.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPEP	ENST00000265162.10 linkuse as main transcript	c.94A>G	p.Ile32Val	missense_variant	1/20	1	NM_001977.4	P1
ENPEP	ENST00000510961.1 linkuse as main transcript	n.73-12033A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4032

AN:

152122

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00709

AC:

1712

AN:

241590

Hom.:

AF XY:

0.00539

AC XY:

699

AN XY:

129764

show subpopulations

Gnomad AFR exome

AF:

0.0918

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00287

AC:

4152

AN:

1445904

Hom.:

181

Cov.:

AF XY:

0.00253

AC XY:

1810

AN XY:

716648

show subpopulations

Gnomad4 AFR exome

AF:

0.0978

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.0266

AC:

4042

AN:

152240

Hom.:

191

Cov.:

AF XY:

0.0265

AC XY:

1973

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0919

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.0304

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0960

AC:

423

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00797

AC:

967

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.64

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.065

Eigen

Benign

-0.15

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.040

REVEL

Benign

0.16

Sift

Benign

0.17

Sift4G

Benign

0.77

Polyphen

0.010

Vest4

0.18

MVP

0.35

MPC

0.092

ClinPred

0.045

GERP RS

5.6

Varity_R

0.029

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over