chr6-12295302-A-G

Position:

• chr6-12295302-A-G

Variant summary

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

The NM_001955.5(EDN1):​c.534-660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,100 control chromosomes in the GnomAD database, including 834 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 0.10 (834 hom., cov: 32)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

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 (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-660A>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.534-660A>G		intron_variant		1	NM_001955.5	ENSP00000368683	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15405 AN: 151982 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.101 AC: 15406 AN: 152100 Hom.: 834 Cov.: 32 AF XY: 0.100 AC XY: 7438 AN XY: 74356

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.111

Alfa AF: 0.105 Hom.: 172

Bravo AF: 0.0978

Asia WGS AF: 0.0380 AC: 132 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	0.13
DANN	Benign	0.25

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: rs6912834; hg19: chr6-12295535;