6-12295228-G-A

Position:

• chr6-12295228-G-A

Variant summary

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

The NM_001955.5(EDN1):​c.534-734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,088 control chromosomes in the GnomAD database, including 3,379 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 (3379 hom., cov: 29)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-734G>A		intron_variant		ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.534-734G>A		intron_variant		1	NM_001955.5	ENSP00000368683	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21223 AN: 151972 Hom.: 3372 Cov.: 29

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.140 AC: 21255 AN: 152088 Hom.: 3379 Cov.: 29 AF XY: 0.134 AC XY: 9995 AN XY: 74350

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0581

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0927 Hom.: 301

Bravo AF: 0.155

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.6
DANN	Benign	0.62

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: rs10478723; hg19: chr6-12295461;