rs141331809

Variant names:

• chr4-147542480-A-G
• rs141331809
• NM_001957.4:c.1146A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001957.4(EDNRA):​c.1146A>G​(p.Ser382Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,614,094 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (30 hom.)
• Consequence: EDNRA NM_001957.4 splice_region, synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.326
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 4-147542480-A-G is Benign according to our data. Variant chr4-147542480-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 711201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.326 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	NM_001957.4	MANE Select	c.1146A>G	p.Ser382Ser	splice_region synonymous	Exon 8 of 8	NP_001948.1	P25101-1
	EDNRA	NM_001166055.2		c.819A>G	p.Ser273Ser	splice_region synonymous	Exon 6 of 6	NP_001159527.1	P25101-4
	EDNRA	NR_045958.2		n.1297A>G		splice_region non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	ENST00000651419.1	MANE Select	c.1146A>G	p.Ser382Ser	splice_region synonymous	Exon 8 of 8	ENSP00000498969.1	P25101-1
	EDNRA	ENST00000324300.10	TSL:1	c.1146A>G	p.Ser382Ser	splice_region synonymous	Exon 8 of 8	ENSP00000315011.5	P25101-1
	EDNRA	ENST00000506066.1	TSL:1	c.819A>G	p.Ser273Ser	splice_region synonymous	Exon 5 of 5	ENSP00000425281.1	P25101-4

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 569 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00500

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00539

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00396 AC: 994 AN: 251192 AF XY: 0.00402

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00347

Gnomad NFE exome AF: 0.00639

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00559 AC: 8169 AN: 1461822 Hom.: 30 Cov.: 31 AF XY: 0.00538 AC XY: 3913 AN XY: 727220

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00268 AC: 120 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00160 AC: 138 AN: 86252

European-Finnish (FIN) AF: 0.00374 AC: 200 AN: 53412

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00663 AC: 7375 AN: 1111966

Other (OTH) AF: 0.00495 AC: 299 AN: 60392

GnomAD4 genome AF: 0.00374 AC: 569 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00347 AC XY: 258 AN XY: 74450

African (AFR) AF: 0.00108 AC: 45 AN: 41540

American (AMR) AF: 0.00588 AC: 90 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00500 AC: 53 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00539 AC: 367 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00483 Hom.: 2

Bravo AF: 0.00371

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00539

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	EDNRA-related disorder (1)
-	-	1	Migraine with or without aura, susceptibility to, 1;C4225349:Mandibulofacial dysostosis with alopecia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.96
DANN	Benign	0.75
PhyloP100		-0.33
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs141331809; hg19: chr4-148463632;