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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001957.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDNRA	NM_001957.4	MANE Select	c.420+2019T>A	intron	N/A	NP_001948.1	P25101-1
EDNRA	NM_001166055.2		c.420+2019T>A	intron	N/A	NP_001159527.1	P25101-4
EDNRA	NM_001354797.2		c.420+2019T>A	intron	N/A	NP_001341726.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDNRA	ENST00000651419.1	MANE Select	c.420+2019T>A	intron	N/A	ENSP00000498969.1	P25101-1
EDNRA	ENST00000324300.10	TSL:1	c.420+2019T>A	intron	N/A	ENSP00000315011.5	P25101-1
EDNRA	ENST00000506066.1	TSL:1	c.420+2019T>A	intron	N/A	ENSP00000425281.1	P25101-4

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over