Variant chr20-59300989-C-T 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_207034.3(EDN3):c.52+125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,152,400 control chromosomes in the GnomAD database, including 2,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 534 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2011 hom. )

Consequence

EDN3
NM_207034.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.247

Variant links:

Genes affected

EDN3 (HGNC:3178): (endothelin 3) The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety of biological functions. The active form of this protein is a 21 amino acid peptide processed from the precursor protein. The active peptide is a ligand for endothelin receptor type B (EDNRB). The interaction of this endothelin with EDNRB is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. Mutations in this gene and EDNRB have been associated with Hirschsprung disease (HSCR) and Waardenburg syndrome (WS), which are congenital disorders involving neural crest-derived cells. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

EDN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-59300989-C-T is Benign according to our data. Variant chr20-59300989-C-T is described in ClinVar as [Benign]. Clinvar id is 1291826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN3	NM_207034.3 linkuse as main transcript	c.52+125C>T		intron_variant		ENST00000337938.7	NP_996917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN3	ENST00000337938.7 linkuse as main transcript	c.52+125C>T		intron_variant		1	NM_207034.3	ENSP00000337128	A2	P14138-1

Frequencies

GnomAD3 genomes

AF:

0.0745

AC:

11328

AN:

152144

Hom.:

532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0600

Gnomad OTH

AF:

0.0884

GnomAD4 exome

AF:

0.0583

AC:

58313

AN:

1000136

Hom.:

2011

AF XY:

0.0593

AC XY:

29801

AN XY:

502862

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0371

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.000296

Gnomad4 SAS exome

AF:

0.0808

Gnomad4 FIN exome

AF:

0.0487

Gnomad4 NFE exome

AF:

0.0574

Gnomad4 OTH exome

AF:

0.0637

GnomAD4 genome

AF:

0.0745

AC:

11341

AN:

152264

Hom.:

534

Cov.:

AF XY:

0.0733

AC XY:

5460

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0467

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0799

Gnomad4 FIN

AF:

0.0431

Gnomad4 NFE

AF:

0.0600

Gnomad4 OTH

AF:

0.0875

Alfa

AF:

0.0444

Hom.:

Bravo

AF:

0.0750

Asia WGS

AF:

0.0390

AC:

135

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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