rs11210278

Positions:

• chr1-41484301-C-T

Variant summary

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

The NM_001956.5(EDN2):​c.65-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,458,372 control chromosomes in the GnomAD database, including 23,996 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 (2027 hom., cov: 34)
  • Exomes 𝑓: 0.18 (21969 hom.)
• Consequence: EDN2 NM_001956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

EDN2 (HGNC:3177): (endothelin 2) This gene encodes a member of the endothelin protein family of secretory vasoconstrictive peptides. The preproprotein is processed to a short mature form which functions as a ligand for the endothelin receptors that initiate intracellular signaling events. This gene product is involved in a wide range of biological processes, such as hypertension and ovulation. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN2	NM_001956.5	c.65-98G>A		intron_variant		ENST00000372587.5	NP_001947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN2	ENST00000372587.5	c.65-98G>A		intron_variant		1	NM_001956.5	ENSP00000361668	P1
EDN2	ENST00000490783.5	n.137-189G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21882 AN: 152064 Hom.: 2025 Cov.: 34

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.178 AC: 232128 AN: 1306190 Hom.: 21969 AF XY: 0.177 AC XY: 113297 AN XY: 640542

Gnomad4 AFR exome AF: 0.0390

Gnomad4 AMR exome AF: 0.0974

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.144 AC: 21890 AN: 152182 Hom.: 2027 Cov.: 34 AF XY: 0.147 AC XY: 10907 AN XY: 74406

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.160

Alfa AF: 0.154 Hom.: 300

Bravo AF: 0.131

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.033
DANN	Benign	0.55

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: rs11210278; hg19: chr1-41949972; COSMIC: COSV65423534; COSMIC: COSV65423534;