ENST00000971814.1:c.-422A>C

Variant names:

• chr6-12289406-A-C
• rs3087459
• ENST00000971814.1:c.-422A>C

Variant summary

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

The ENST00000971814.1(EDN1):​c.-422A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,964 control chromosomes in the GnomAD database, including 3,156 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 0.20 (3156 hom., cov: 32)
• Consequence: EDN1 ENST00000971814.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895
• Publications: 23 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: Labcorp Genetics (formerly Invitae), G2P
• auriculocondylar syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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 (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000971814.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDN1	NM_001416564.1		c.-1-1223A>C		intron	N/A	NP_001403493.1	Q6FH53
	EDN1	NM_001416565.1		c.-1-1223A>C		intron	N/A	NP_001403494.1	P05305

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDN1	ENST00000971814.1		c.-422A>C		5_prime_UTR	Exon 1 of 6	ENSP00000641873.1
	EDN1	ENST00000971811.1		c.-2+911A>C		intron	N/A	ENSP00000641870.1
	EDN1	ENST00000877364.1		c.-2+911A>C		intron	N/A	ENSP00000547423.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30175 AN: 151846 Hom.: 3160 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.199 AC: 30177 AN: 151964 Hom.: 3156 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74270

African (AFR) AF: 0.244 AC: 10087 AN: 41402

American (AMR) AF: 0.142 AC: 2163 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3464

East Asian (EAS) AF: 0.218 AC: 1121 AN: 5150

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4818

European-Finnish (FIN) AF: 0.214 AC: 2264 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11801 AN: 67968

Other (OTH) AF: 0.173 AC: 365 AN: 2108

Alfa AF: 0.190 Hom.: 1123

Bravo AF: 0.192

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.50
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs3087459; hg19: chr6-12289639;