rs6912834

Variant names:

• chr6-12295302-A-G
• rs6912834
• NM_001955.5:c.534-660A>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.534-660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,100 control chromosomes in the GnomAD database, including 834 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 0.10 (834 hom., cov: 32)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-660A>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.534-660A>G		intron_variant	Intron 4 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+15879T>C		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-4506T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15405 AN: 151982 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.101 AC: 15406 AN: 152100 Hom.: 834 Cov.: 32 AF XY: 0.100 AC XY: 7438 AN XY: 74356

African (AFR) AF: 0.0913 AC: 3790 AN: 41492

American (AMR) AF: 0.0817 AC: 1248 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 526 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5180

South Asian (SAS) AF: 0.0669 AC: 322 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1271 AN: 10568

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7827 AN: 67992

Other (OTH) AF: 0.111 AC: 235 AN: 2108

Alfa AF: 0.105 Hom.: 173

Bravo AF: 0.0978

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.25
PhyloP100		-3.3
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: rs6912834; hg19: chr6-12295535;