6-12292295-G-A

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.65-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,609,308 control chromosomes in the GnomAD database, including 4,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1630 hom., cov: 33)
  • Exomes 𝑓: 0.049 (3026 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412

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=-0.82).
• BP6: Variant 6-12292295-G-A is Benign according to our data. Variant chr6-12292295-G-A is described in ClinVar as [Benign]. Clinvar id is 1232026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.65-46G>A		intron_variant		ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.65-46G>A		intron_variant		1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15775 AN: 152116 Hom.: 1625 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0980

GnomAD3 exomes AF: 0.0557 AC: 13722 AN: 246412 Hom.: 905 AF XY: 0.0531 AC XY: 7100 AN XY: 133834

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0585

Gnomad EAS exome AF: 0.00104

Gnomad SAS exome AF: 0.0584

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0443

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0492 AC: 71664 AN: 1457074 Hom.: 3026 Cov.: 32 AF XY: 0.0489 AC XY: 35489 AN XY: 725098

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.0374

Gnomad4 ASJ exome AF: 0.0586

Gnomad4 EAS exome AF: 0.000605

Gnomad4 SAS exome AF: 0.0586

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.0592

GnomAD4 genome AF: 0.104 AC: 15800 AN: 152234 Hom.: 1630 Cov.: 33 AF XY: 0.0999 AC XY: 7440 AN XY: 74440

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.0587 Hom.: 555

Bravo AF: 0.113

Asia WGS AF: 0.0420 AC: 148 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
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: rs1800542; hg19: chr6-12292528;