NM_001955.5:c.534-692A>G

Variant names:

• chr6-12295270-A-G
• rs1626492
• NM_001955.5:c.534-692A>G

Variant summary

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

The NM_001955.5(EDN1):​c.534-692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,998 control chromosomes in the GnomAD database, including 33,770 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 0.64 (33770 hom., cov: 31)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 11 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-692A>G		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.534-692A>G		intron_variant	Intron 4 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+15911T>C		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-4474T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97715 AN: 151878 Hom.: 33748 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.643 AC: 97771 AN: 151998 Hom.: 33770 Cov.: 31 AF XY: 0.653 AC XY: 48532 AN XY: 74272

African (AFR) AF: 0.374 AC: 15498 AN: 41430

American (AMR) AF: 0.752 AC: 11490 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3468

East Asian (EAS) AF: 0.956 AC: 4953 AN: 5180

South Asian (SAS) AF: 0.820 AC: 3949 AN: 4818

European-Finnish (FIN) AF: 0.774 AC: 8168 AN: 10554

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49123 AN: 67968

Other (OTH) AF: 0.649 AC: 1367 AN: 2106

Alfa AF: 0.699 Hom.: 61414

Bravo AF: 0.627

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		1.4
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: rs1626492; hg19: chr6-12295503;