chr4-147542688-G-C

Variant names:

• chr4-147542688-G-C
• rs5335
• ENST00000510697.5:n.*591G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000510697.5(EDNRA):​n.*591G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,558,976 control chromosomes in the GnomAD database, including 155,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21758 hom., cov: 31)
  • Exomes 𝑓: 0.43 (133444 hom.)
• Consequence: EDNRA ENST00000510697.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238
• Publications: 62 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-147542688-G-C is Benign according to our data. Variant chr4-147542688-G-C is described in ClinVar as Benign. ClinVar VariationId is 1297294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510697.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	NM_001957.4	MANE Select	c.*70G>C		3_prime_UTR	Exon 8 of 8	NP_001948.1
	EDNRA	NR_045958.2		n.1505G>C		non_coding_transcript_exon	Exon 7 of 7
	EDNRA	NR_148963.2		n.1214G>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRA	ENST00000510697.5	TSL:1	n.*591G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000427259.1
	EDNRA	ENST00000651419.1	MANE Select	c.*70G>C		3_prime_UTR	Exon 8 of 8	ENSP00000498969.1
	EDNRA	ENST00000324300.10	TSL:1	c.*70G>C		3_prime_UTR	Exon 8 of 8	ENSP00000315011.5

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78185 AN: 151898 Hom.: 21713 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.428 AC: 601541 AN: 1406960 Hom.: 133444 Cov.: 24 AF XY: 0.434 AC XY: 302037 AN XY: 695846

African (AFR) AF: 0.739 AC: 23864 AN: 32310

American (AMR) AF: 0.495 AC: 19917 AN: 40272

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 12339 AN: 24352

East Asian (EAS) AF: 0.482 AC: 18689 AN: 38806

South Asian (SAS) AF: 0.664 AC: 52542 AN: 79152

European-Finnish (FIN) AF: 0.357 AC: 16911 AN: 47374

Middle Eastern (MID) AF: 0.556 AC: 3115 AN: 5602

European-Non Finnish (NFE) AF: 0.396 AC: 427535 AN: 1080648

Other (OTH) AF: 0.456 AC: 26629 AN: 58444

GnomAD4 genome AF: 0.515 AC: 78283 AN: 152016 Hom.: 21758 Cov.: 31 AF XY: 0.520 AC XY: 38642 AN XY: 74302

African (AFR) AF: 0.727 AC: 30147 AN: 41468

American (AMR) AF: 0.520 AC: 7957 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1744 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2303 AN: 5152

South Asian (SAS) AF: 0.670 AC: 3224 AN: 4812

European-Finnish (FIN) AF: 0.371 AC: 3921 AN: 10572

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27508 AN: 67938

Other (OTH) AF: 0.517 AC: 1090 AN: 2110

Alfa AF: 0.299 Hom.: 714

Bravo AF: 0.527

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20100616, 20028935)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.2
DANN	Benign	0.57
PhyloP100		-0.24
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: rs5335; hg19: chr4-148463840; COSMIC: COSV60096301;