4-147542688-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000510697.5(EDNRA):​n.*591G>A 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 0.00000142 in 1,408,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EDNRA ENST00000510697.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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>A		3_prime_UTR	Exon 8 of 8	NP_001948.1
	EDNRA	NR_045958.2		n.1505G>A		non_coding_transcript_exon	Exon 7 of 7
	EDNRA	NR_148963.2		n.1214G>A		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>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000427259.1
	EDNRA	ENST00000651419.1	MANE Select	c.*70G>A		3_prime_UTR	Exon 8 of 8	ENSP00000498969.1
	EDNRA	ENST00000324300.10	TSL:1	c.*70G>A		3_prime_UTR	Exon 8 of 8	ENSP00000315011.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408826 Hom.: 0 Cov.: 24 AF XY: 0.00000287 AC XY: 2 AN XY: 696762

African (AFR) AF: 0.00 AC: 0 AN: 32360

American (AMR) AF: 0.00 AC: 0 AN: 40384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24386

East Asian (EAS) AF: 0.00 AC: 0 AN: 38858

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081956

Other (OTH) AF: 0.00 AC: 0 AN: 58512

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.94
PhyloP100		-0.24

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;