chr20-59301185-G-T

Position:

• chr20-59301185-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207034.3(EDN3):​c.53-225G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,290 control chromosomes in the GnomAD database, including 1,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1988 hom., cov: 33)
• Consequence: EDN3 NM_207034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.282

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-59301185-G-T is Benign according to our data. Variant chr20-59301185-G-T is described in ClinVar as [Benign]. Clinvar id is 1178568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN3	NM_207034.3	c.53-225G>T		intron_variant		ENST00000337938.7	NP_996917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN3	ENST00000337938.7	c.53-225G>T		intron_variant		1	NM_207034.3	ENSP00000337128	A2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20848 AN: 152172 Hom.: 1966 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20920 AN: 152290 Hom.: 1988 Cov.: 33 AF XY: 0.134 AC XY: 9959 AN XY: 74470

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.135

Alfa AF: 0.114 Hom.: 293

Bravo AF: 0.141

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs149214; hg19: chr20-57876240;