dbSNP rs10305925: EDNRA:c.1034+52T>C (chr4-147540002-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001957.4(EDNRA):c.1034+52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,544,072 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 40 hom. )

Consequence

EDNRA
NM_001957.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.574

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 links:

TMEM184C-DT (HGNC:55544): (TMEM184C divergent transcript)

TMEM184C-DT links:

LOC124900795 (HGNC:):

LOC124900795 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-147540002-T-C is Benign according to our data. Variant chr4-147540002-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 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.1034+52T>C	intron	N/A	NP_001948.1	P25101-1
EDNRA	NM_001166055.2		c.707+52T>C	intron	N/A	NP_001159527.1	P25101-4
EDNRA	NR_045958.2		n.1185+52T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDNRA	ENST00000651419.1	MANE Select	c.1034+52T>C	intron	N/A	ENSP00000498969.1	P25101-1
EDNRA	ENST00000324300.10	TSL:1	c.1034+52T>C	intron	N/A	ENSP00000315011.5	P25101-1
EDNRA	ENST00000506066.1	TSL:1	c.707+52T>C	intron	N/A	ENSP00000425281.1	P25101-4

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2181

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00435

AC:

857

AN:

196822

AF XY:

0.00331

show subpopulations

Gnomad AFR exome

AF:

0.0517

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00151

AC:

2098

AN:

1391804

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

932

AN XY:

688272

show subpopulations

African (AFR)

AF:

0.0531

AC:

1604

AN:

30230

American (AMR)

AF:

0.00316

AC:

AN:

28764

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

22042

East Asian (EAS)

AF:

0.00

AC:

AN:

39040

South Asian (SAS)

AF:

0.0000548

AC:

AN:

72938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50722

Middle Eastern (MID)

AF:

0.00625

AC:

AN:

5278

European-Non Finnish (NFE)

AF:

0.000134

AC:

145

AN:

1085566

Other (OTH)

AF:

0.00343

AC:

196

AN:

57224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

188

281

375

469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0144

AC:

2186

AN:

152268

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1023

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0493

AC:

2049

AN:

41536

American (AMR)

AF:

0.00523

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68014

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00681

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.7

(source)

DANN

Benign

0.38

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism

(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