rs2071943

Variant names:

• chr6-12295581-G-A
• rs2071943
• NM_001955.5:c.534-381G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-12295581-G-A
• chr6-12295581-G-C

Variant summary

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

The NM_001955.5(EDN1):​c.534-381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,884 control chromosomes in the GnomAD database, including 3,466 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 0.21 (3466 hom., cov: 32)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-381G>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.534-381G>A		intron_variant	Intron 4 of 4	1	NM_001955.5	ENSP00000368683.5

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31883 AN: 151768 Hom.: 3468 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.210 AC: 31883 AN: 151884 Hom.: 3466 Cov.: 32 AF XY: 0.212 AC XY: 15730 AN XY: 74186

African (AFR) AF: 0.186 AC: 7694 AN: 41390

American (AMR) AF: 0.171 AC: 2610 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3466

East Asian (EAS) AF: 0.291 AC: 1507 AN: 5170

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4818

European-Finnish (FIN) AF: 0.192 AC: 2014 AN: 10496

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

European-Non Finnish (NFE) AF: 0.217 AC: 14753 AN: 67958

Other (OTH) AF: 0.194 AC: 409 AN: 2104

Alfa AF: 0.215 Hom.: 6073

Bravo AF: 0.204

Asia WGS AF: 0.304 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.44
PhyloP100		-0.86
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: rs2071943; hg19: chr6-12295814;