rs1800543

chr6-12293904-T-C

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.234-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,607,168 control chromosomes in the GnomAD database, including 50,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4586 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45596 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354

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=-0.8).
• BP6: Variant 6-12293904-T-C is Benign according to our data. Variant chr6-12293904-T-C is described in ClinVar as [Benign]. Clinvar id is 1222387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.234-37T>C		intron_variant		ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.234-37T>C		intron_variant		1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36974 AN: 151966 Hom.: 4583 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.252 AC: 61922 AN: 245420 Hom.: 8474 AF XY: 0.259 AC XY: 34595 AN XY: 133380

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.291

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.246 AC: 357815 AN: 1455084 Hom.: 45596 Cov.: 30 AF XY: 0.250 AC XY: 181214 AN XY: 724128

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152084 Hom.: 4586 Cov.: 32 AF XY: 0.246 AC XY: 18290 AN XY: 74328

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.224

Alfa AF: 0.237 Hom.: 1012

Bravo AF: 0.239

Asia WGS AF: 0.320 AC: 1112 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	-0.80
Cadd	Benign	4.8
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1800543; hg19: chr6-12294137; COSMIC: COSV65081057;