rs1800543

Variant names:

• chr6-12293904-T-C
• rs1800543
• NM_001955.5:c.234-37T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001955.5(EDN1):​c.234-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,607,168 control chromosomes in the GnomAD database, including 50,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4586 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45596 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• question mark ears, isolated

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-12293904-T-C is Benign according to our data. Variant chr6-12293904-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.234-37T>C		intron_variant	Intron 2 of 4	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.234-37T>C		intron_variant	Intron 2 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+17277A>G		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-3108A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36974 AN: 151966 Hom.: 4583 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.252 AC: 61922 AN: 245420 AF XY: 0.259

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.246 AC: 357815 AN: 1455084 Hom.: 45596 Cov.: 30 AF XY: 0.250 AC XY: 181214 AN XY: 724128

African (AFR) AF: 0.244 AC: 8135 AN: 33314

American (AMR) AF: 0.200 AC: 8899 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 6174 AN: 26082

East Asian (EAS) AF: 0.289 AC: 11465 AN: 39608

South Asian (SAS) AF: 0.403 AC: 34658 AN: 85916

European-Finnish (FIN) AF: 0.218 AC: 11589 AN: 53170

Middle Eastern (MID) AF: 0.252 AC: 1443 AN: 5728

European-Non Finnish (NFE) AF: 0.235 AC: 260125 AN: 1106528

Other (OTH) AF: 0.255 AC: 15327 AN: 60164

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152084 Hom.: 4586 Cov.: 32 AF XY: 0.246 AC XY: 18290 AN XY: 74328

African (AFR) AF: 0.246 AC: 10186 AN: 41462

American (AMR) AF: 0.236 AC: 3604 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1554 AN: 5164

South Asian (SAS) AF: 0.404 AC: 1944 AN: 4808

European-Finnish (FIN) AF: 0.218 AC: 2309 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15850 AN: 67986

Other (OTH) AF: 0.224 AC: 473 AN: 2116

Alfa AF: 0.233 Hom.: 1572

Bravo AF: 0.239

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.58
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1800543; hg19: chr6-12294137; COSMIC: COSV65081057;