rs10305924

Variant names:

• chr4-147539969-G-A
• rs10305924
• NM_001957.4:c.1034+19G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-147539969-G-A
• chr4-147539969-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001957.4(EDNRA):​c.1034+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,560,856 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (8 hom.)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.507
• Publications: 2 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)

LOC124900795 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-147539969-G-A is Benign according to our data. Variant chr4-147539969-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1654745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 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.1034+19G>A		intron	N/A	NP_001948.1	P25101-1
	EDNRA	NM_001166055.2		c.707+19G>A		intron	N/A	NP_001159527.1	P25101-4
	EDNRA	NR_045958.2		n.1185+19G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	ENST00000651419.1	MANE Select	c.1034+19G>A		intron	N/A	ENSP00000498969.1	P25101-1
	EDNRA	ENST00000324300.10	TSL:1	c.1034+19G>A		intron	N/A	ENSP00000315011.5	P25101-1
	EDNRA	ENST00000506066.1	TSL:1	c.707+19G>A		intron	N/A	ENSP00000425281.1	P25101-4

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 492 AN: 152046 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00516

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00241 AC: 505 AN: 209670 AF XY: 0.00239

Gnomad AFR exome AF: 0.000990

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000126

Gnomad FIN exome AF: 0.00201

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00333 AC: 4690 AN: 1408692 Hom.: 8 Cov.: 31 AF XY: 0.00328 AC XY: 2291 AN XY: 698176

African (AFR) AF: 0.000790 AC: 24 AN: 30388

American (AMR) AF: 0.00134 AC: 41 AN: 30556

Ashkenazi Jewish (ASJ) AF: 0.0000857 AC: 2 AN: 23346

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39130

South Asian (SAS) AF: 0.00182 AC: 140 AN: 77032

European-Finnish (FIN) AF: 0.00188 AC: 98 AN: 52024

Middle Eastern (MID) AF: 0.000544 AC: 3 AN: 5514

European-Non Finnish (NFE) AF: 0.00385 AC: 4212 AN: 1092844

Other (OTH) AF: 0.00290 AC: 168 AN: 57858

GnomAD4 genome AF: 0.00323 AC: 492 AN: 152164 Hom.: 1 Cov.: 32 AF XY: 0.00344 AC XY: 256 AN XY: 74372

African (AFR) AF: 0.000795 AC: 33 AN: 41516

American (AMR) AF: 0.00327 AC: 50 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4806

European-Finnish (FIN) AF: 0.00397 AC: 42 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00516 AC: 351 AN: 68014

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00272 Hom.: 1

Bravo AF: 0.00252

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.013
DANN	Benign	0.61
PhyloP100		-0.51
Mutation Taster		=100/0	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: rs10305924; hg19: chr4-148461121;