rs7655670

Variant names:

• chr4-147502686-T-C
• rs7655670
• NM_001957.4:c.420+16585T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-147502686-T-C
• chr4-147502686-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001957.4(EDNRA):​c.420+16585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,090 control chromosomes in the GnomAD database, including 14,982 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 0.42 (14982 hom., cov: 33)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 3 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	NM_001957.4	MANE Select	c.420+16585T>C		intron	N/A	NP_001948.1	P25101-1
	EDNRA	NM_001166055.2		c.420+16585T>C		intron	N/A	NP_001159527.1	P25101-4
	EDNRA	NM_001354797.2		c.420+16585T>C		intron	N/A	NP_001341726.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	ENST00000651419.1	MANE Select	c.420+16585T>C		intron	N/A	ENSP00000498969.1	P25101-1
	EDNRA	ENST00000324300.10	TSL:1	c.420+16585T>C		intron	N/A	ENSP00000315011.5	P25101-1
	EDNRA	ENST00000506066.1	TSL:1	c.420+16585T>C		intron	N/A	ENSP00000425281.1	P25101-4

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63221 AN: 151972 Hom.: 14958 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 63289 AN: 152090 Hom.: 14982 Cov.: 33 AF XY: 0.412 AC XY: 30629 AN XY: 74348

African (AFR) AF: 0.657 AC: 27238 AN: 41480

American (AMR) AF: 0.341 AC: 5209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1584 AN: 5190

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4816

European-Finnish (FIN) AF: 0.265 AC: 2810 AN: 10588

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21592 AN: 67948

Other (OTH) AF: 0.405 AC: 853 AN: 2108

Alfa AF: 0.313 Hom.: 2631

Bravo AF: 0.431

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.31
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs7655670; hg19: chr4-148423838; COSMIC: COSV107405236; COSMIC: COSV107405236;