rs1626492

Positions:

• chr6-12295270-A-G
• chr6-12295270-A-T

Variant summary

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

The NM_001955.5(EDN1):​c.534-692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,998 control chromosomes in the GnomAD database, including 33,770 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 0.64 (33770 hom., cov: 31)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-692A>G		intron_variant		ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.534-692A>G		intron_variant		1	NM_001955.5	ENSP00000368683	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97715 AN: 151878 Hom.: 33748 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.643 AC: 97771 AN: 151998 Hom.: 33770 Cov.: 31 AF XY: 0.653 AC XY: 48532 AN XY: 74272

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.649

Alfa AF: 0.708 Hom.: 43258

Bravo AF: 0.627

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.82

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: rs1626492; hg19: chr6-12295503;