6-12290495-TAA-TA

Position:

• chr6-12290495-TAA-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001955.5(EDN1):​c.-131delA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (44940 hom., cov: 0)
  • Exomes 𝑓: 0.75 (171476 hom.)
• Consequence: EDN1 NM_001955.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN1	NM_001955.5	c.-131delA		5_prime_UTR_variant	1/5	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375	c.-131delA		5_prime_UTR_variant	1/5	1	NM_001955.5	ENSP00000368683.5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116729 AN: 152102 Hom.: 44887 Cov.: 0

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.754 AC: 451815 AN: 599158 Hom.: 171476 Cov.: 0 AF XY: 0.756 AC XY: 241912 AN XY: 320080

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.723

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.824

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.768 AC: 116841 AN: 152222 Hom.: 44940 Cov.: 0 AF XY: 0.771 AC XY: 57369 AN XY: 74426

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.736

Alfa AF: 0.757 Hom.: 5301

Bravo AF: 0.767

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs1800997; hg19: chr6-12290728;