rs3087459

Variant names:

• chr6-12289406-A-C
• rs3087459
• NM_001416564.1:c.-1-1223A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001416564.1(EDN1):​c.-1-1223A>C variant causes a intron 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 NM_001416564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001416564.1	c.-1-1223A>C		intron_variant	Intron 1 of 5		NP_001403493.1
EDN1	NM_001416565.1	c.-1-1223A>C		intron_variant	Intron 3 of 7		NP_001403494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.173

Alfa AF: 0.189 Hom.: 617

Bravo AF: 0.192

Asia WGS AF: 0.287 AC: 997 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	5.3
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3087459; hg19: chr6-12289639;