rs9296344

Positions:

• chr6-12296795-T-C

Variant summary

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

The NM_001955.5(EDN1):​c.*728T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,238 control chromosomes in the GnomAD database, including 2,991 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 0.14 (2990 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: EDN1 NM_001955.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.850

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.*728T>C		3_prime_UTR_variant	5/5	ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.*728T>C		3_prime_UTR_variant	5/5	1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21547 AN: 151986 Hom.: 2979 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.104 AC: 14 AN: 134 Hom.: 1 Cov.: 0 AF XY: 0.0962 AC XY: 5 AN XY: 52

Gnomad4 AMR exome AF: 0.111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.142 AC: 21581 AN: 152104 Hom.: 2990 Cov.: 32 AF XY: 0.137 AC XY: 10206 AN XY: 74374

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.0745

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0779 Hom.: 1054

Bravo AF: 0.156

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.9
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs9296344; hg19: chr6-12297028; COSMIC: COSV105313152;