dbSNP rs702757: EDNRA:c.420+2019T>A (chr4-147488120-T-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.420+2019T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,008 control chromosomes in the GnomAD database, including 12,340 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 0.38 ( 12338 hom., cov: 32)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

EDNRA
NM_001957.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

2 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:

ENSG00000280219 (HGNC:):

ENSG00000280219 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRA	NM_001957.4 link	c.420+2019T>A		intron_variant	Intron 2 of 7	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.420+2019T>A		intron_variant	Intron 2 of 7		NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57768

AN:

151880

Hom.:

12316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.370

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.381

AC:

57838

AN:

151998

Hom.:

12338

Cov.:

AF XY:

0.376

AC XY:

27953

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.585

AC:

24231

AN:

41420

American (AMR)

AF:

0.315

AC:

4804

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1256

AN:

3468

East Asian (EAS)

AF:

0.328

AC:

1697

AN:

5174

South Asian (SAS)

AF:

0.411

AC:

1984

AN:

4824

European-Finnish (FIN)

AF:

0.239

AC:

2523

AN:

10576

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.296

AC:

20113

AN:

67954

Other (OTH)

AF:

0.369

AC:

780

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1728

3456

5184

6912

8640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.161

Hom.:

280

Bravo

AF:

0.396

Asia WGS

AF:

0.410

AC:

1424

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.46

(source)

DANN

Benign

0.79

PhyloP100

-0.66

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