Variant rs5370 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001955.5(EDN1):c.594G>T(p.Lys198Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,552 control chromosomes in the GnomAD database, including 43,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3521 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39731 hom. )

Consequence

EDN1
NM_001955.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0700

Variant links:

Genes affected

EDN1 (HGNC:3176): (endothelin 1) This gene encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. Aberrant expression of this gene may promote tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

EDN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002188623).

BP6

Variant 6-12296022-G-T is Benign according to our data. Variant chr6-12296022-G-T is described in ClinVar as [Benign]. Clinvar id is 16652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5 link	c.594G>T	p.Lys198Asn	missense_variant	Exon 5 of 5	ENST00000379375.6	NP_001946.3	P05305Q6FH53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6 link	c.594G>T	p.Lys198Asn	missense_variant	Exon 5 of 5	1	NM_001955.5	ENSP00000368683.5		P05305

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32244

AN:

151840

Hom.:

3523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.229

AC:

57654

AN:

251452

Hom.:

7480

AF XY:

0.239

AC XY:

32545

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.227

AC:

331748

AN:

1461594

Hom.:

39731

Cov.:

AF XY:

0.232

AC XY:

168849

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.212

AC:

32242

AN:

151958

Hom.:

3521

Cov.:

AF XY:

0.214

AC XY:

15904

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.219

Hom.:

9631

Bravo

AF:

0.207

TwinsUK

AF:

0.217

AC:

804

ALSPAC

AF:

0.219

AC:

845

ESP6500AA

AF:

0.196

AC:

865

ESP6500EA

AF:

0.211

AC:

1817

ExAC

AF:

0.234

AC:

28467

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2025	- -

Auriculocondylar syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

High density lipoprotein cholesterol level quantitative trait locus 7

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.89

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Uncertain

0.025

Polyphen

0.45

Vest4

0.037

MutPred

0.078

Loss of methylation at K198 (P = 0.0204);

MPC

0.26

ClinPred

0.0022

GERP RS

2.2

Varity_R

0.10

gMVP

0.054

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