rs2071942

Variant names:

• chr6-12294760-G-A
• rs2071942
• NM_001955.5:c.533+356G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001955.5(EDN1):​c.533+356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,934 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3926 hom., cov: 31)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.533+356G>A		intron_variant	Intron 4 of 4	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.533+356G>A		intron_variant	Intron 4 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+16421C>T		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-3964C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34072 AN: 151816 Hom.: 3928 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.224 AC: 34073 AN: 151934 Hom.: 3926 Cov.: 31 AF XY: 0.228 AC XY: 16905 AN XY: 74246

African (AFR) AF: 0.194 AC: 8044 AN: 41432

American (AMR) AF: 0.227 AC: 3469 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1508 AN: 5158

South Asian (SAS) AF: 0.407 AC: 1957 AN: 4810

European-Finnish (FIN) AF: 0.197 AC: 2073 AN: 10534

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15541 AN: 67954

Other (OTH) AF: 0.204 AC: 430 AN: 2104

Alfa AF: 0.227 Hom.: 509

Bravo AF: 0.219

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071942; hg19: chr6-12294993;