6-12292539-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001955.5(EDN1):c.233+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,612,970 control chromosomes in the GnomAD database, including 169,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12380 hom., cov: 33)
  • Exomes 𝑓: 0.46 (156829 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.267

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-12292539-G-T is Benign according to our data. Variant chr6-12292539-G-T is described in ClinVar as [Benign]. Clinvar id is 1274781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.233+30G>T		intron_variant		ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.233+30G>T		intron_variant		1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55731 AN: 152000 Hom.: 12367 Cov.: 33

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.451 AC: 113343 AN: 251142 Hom.: 27186 AF XY: 0.454 AC XY: 61620 AN XY: 135766

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.547

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.458 AC: 668873 AN: 1460854 Hom.: 156829 Cov.: 35 AF XY: 0.457 AC XY: 332213 AN XY: 726790

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.366 AC: 55743 AN: 152116 Hom.: 12380 Cov.: 33 AF XY: 0.374 AC XY: 27780 AN XY: 74364

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.391

Alfa AF: 0.430 Hom.: 16268

Bravo AF: 0.349

Asia WGS AF: 0.456 AC: 1582 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.80

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: rs2070699; hg19: chr6-12292772; COSMIC: COSV65080425;