chr4-147530682-G-A

Variant names:

• chr4-147530682-G-A
• rs2048894
• NM_001957.4:c.549-1824G>A

Variant summary

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

The NM_001957.4(EDNRA):​c.549-1824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,030 control chromosomes in the GnomAD database, including 10,900 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 0.35 (10900 hom., cov: 32)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900795 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRA	NM_001957.4	c.549-1824G>A		intron_variant	Intron 3 of 7	ENST00000651419.1	NP_001948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1	c.549-1824G>A		intron_variant	Intron 3 of 7		NM_001957.4	ENSP00000498969.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52538 AN: 151910 Hom.: 10883 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.346 AC: 52587 AN: 152030 Hom.: 10900 Cov.: 32 AF XY: 0.340 AC XY: 25283 AN XY: 74308

African (AFR) AF: 0.585 AC: 24246 AN: 41454

American (AMR) AF: 0.301 AC: 4599 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1077 AN: 5164

South Asian (SAS) AF: 0.337 AC: 1620 AN: 4814

European-Finnish (FIN) AF: 0.177 AC: 1865 AN: 10552

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17044 AN: 67980

Other (OTH) AF: 0.334 AC: 705 AN: 2112

Alfa AF: 0.306 Hom.: 3302

Bravo AF: 0.367

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.060
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: rs2048894; hg19: chr4-148451834; COSMIC: COSV107405244; COSMIC: COSV107405244;