dbSNP rs1801708: EDNRA:c.-230G>A (chr4-147481217-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001957.4(EDNRA):c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,706 control chromosomes in the GnomAD database, including 20,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.46 ( 20282 hom., cov: 32)

Exomes 𝑓: 0.39 ( 45 hom. )

Consequence

EDNRA
NM_001957.4 5_prime_UTR

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 1.56

Publications

14 publications found

Variant links:

Genes affected

EDNRA (HGNC:3179): (endothelin receptor type A) This gene encodes the receptor for endothelin-1, a peptide that plays a role in potent and long-lasting vasoconstriction. This receptor associates with guanine-nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. Polymorphisms in this gene have been linked to migraine headache resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

EDNRA Gene-Disease associations (from GenCC):

mandibulofacial dysostosis with alopecia
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EDNRA 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRA	NM_001957.4 link	c.-230G>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000651419.1	NP_001948.1	P25101-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1 link	c.-230G>A		5_prime_UTR_variant	Exon 1 of 8		NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69175

AN:

151974

Hom.:

20229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.390

AC:

240

AN:

616

Hom.:

Cov.:

AF XY:

0.384

AC XY:

132

AN XY:

344

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.417

AC:

165

AN:

396

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.299

AC:

AN:

184

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.456

AC:

69289

AN:

152090

Hom.:

20282

Cov.:

AF XY:

0.449

AC XY:

33403

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.841

AC:

34932

AN:

41512

American (AMR)

AF:

0.340

AC:

5199

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1287

AN:

3470

East Asian (EAS)

AF:

0.327

AC:

1669

AN:

5104

South Asian (SAS)

AF:

0.438

AC:

2107

AN:

4816

European-Finnish (FIN)

AF:

0.242

AC:

2560

AN:

10594

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20164

AN:

67982

Other (OTH)

AF:

0.435

AC:

918

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1482

2964

4447

5929

7411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.352

Hom.:

14442

Bravo

AF:

0.481

Asia WGS

AF:

0.439

AC:

1524

AN:

3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Migraine, resistance to

Benign:1

May 22, 2001

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.6

PromoterAI

0.15

Neutral

(source)

Mutation Taster

=300/0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over