Variant 6-12294025-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001955.5(EDN1):c.318A>G(p.Glu106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,614,152 control chromosomes in the GnomAD database, including 636,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59329 hom., cov: 33)

Exomes 𝑓: 0.89 ( 576812 hom. )

Consequence

EDN1
NM_001955.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.442

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-12294025-A-G is Benign according to our data. Variant chr6-12294025-A-G is described in ClinVar as [Benign]. Clinvar id is 1255370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.442 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5 linkuse as main transcript	c.318A>G	p.Glu106=	synonymous_variant	3/5	ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6 linkuse as main transcript	c.318A>G	p.Glu106=	synonymous_variant	3/5	1	NM_001955.5	P1

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134308

AN:

152168

Hom.:

59299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.974

Gnomad SAS

AF:

0.946

Gnomad FIN

AF:

0.912

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.879

GnomAD3 exomes

AF:

0.904

AC:

227390

AN:

251448

Hom.:

103033

AF XY:

0.905

AC XY:

123006

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.931

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.976

Gnomad SAS exome

AF:

0.952

Gnomad FIN exome

AF:

0.913

Gnomad NFE exome

AF:

0.879

Gnomad OTH exome

AF:

0.884

GnomAD4 exome

AF:

0.888

AC:

1297864

AN:

1461866

Hom.:

576812

Cov.:

AF XY:

0.890

AC XY:

646907

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.852

Gnomad4 AMR exome

AF:

0.927

Gnomad4 ASJ exome

AF:

0.891

Gnomad4 EAS exome

AF:

0.977

Gnomad4 SAS exome

AF:

0.952

Gnomad4 FIN exome

AF:

0.914

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.888

GnomAD4 genome

AF:

0.883

AC:

134396

AN:

152286

Hom.:

59329

Cov.:

AF XY:

0.886

AC XY:

65991

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.853

Gnomad4 AMR

AF:

0.905

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.974

Gnomad4 SAS

AF:

0.946

Gnomad4 FIN

AF:

0.912

Gnomad4 NFE

AF:

0.880

Gnomad4 OTH

AF:

0.880

Alfa

AF:

0.880

Hom.:

44309

Bravo

AF:

0.878

Asia WGS

AF:

0.928

AC:

3225

AN:

3478

EpiCase

AF:

0.867

EpiControl

AF:

0.869

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Auriculocondylar syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

DANN

Benign

0.36

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