dbSNP rs11210278: EDN2:c.65-98G>A (chr1-41484301-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19

Publications

8 publications found

Variant links:

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]

EDN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EDN2	NM_001956.5 link	c.65-98G>A		intron_variant	Intron 1 of 4	ENST00000372587.5	NP_001947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN2	ENST00000372587.5 link	c.65-98G>A		intron_variant	Intron 1 of 4	1	NM_001956.5	ENSP00000361668.4

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21882

AN:

152064

Hom.:

2025

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0390

AC:

1163

AN:

29806

American (AMR)

AF:

0.0974

AC:

3188

AN:

32734

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

2940

AN:

21506

East Asian (EAS)

AF:

0.347

AC:

12378

AN:

35652

South Asian (SAS)

AF:

0.149

AC:

10406

AN:

69724

European-Finnish (FIN)

AF:

0.220

AC:

10086

AN:

45810

Middle Eastern (MID)

AF:

0.118

AC:

441

AN:

3730

European-Non Finnish (NFE)

AF:

0.180

AC:

182353

AN:

1012836

Other (OTH)

AF:

0.169

AC:

9173

AN:

54392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9554

19109

28663

38218

47772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6470

12940

19410

25880

32350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.144

AC:

21890

AN:

152182

Hom.:

2027

Cov.:

AF XY:

0.147

AC XY:

10907

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0420

AC:

1747

AN:

41558

American (AMR)

AF:

0.124

AC:

1903

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

493

AN:

3470

East Asian (EAS)

AF:

0.327

AC:

1684

AN:

5150

South Asian (SAS)

AF:

0.150

AC:

726

AN:

4830

European-Finnish (FIN)

AF:

0.223

AC:

2365

AN:

10586

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12392

AN:

67974

Other (OTH)

AF:

0.160

AC:

338

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

959

1918

2878

3837

4796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.55

PhyloP100

-2.2

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over