19-46621457-T-G

Variant names:

• chr19-46621457-T-G
• rs2229129
• NM_000960.4:c.984A>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000960.4(PTGIR):​c.984A>C​(p.Ser328Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,613,728 control chromosomes in the GnomAD database, including 132,297 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 0.40 (12484 hom., cov: 33)
  • Exomes 𝑓: 0.40 (119813 hom.)
• Consequence: PTGIR NM_000960.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.59

Genes affected

PTGIR (HGNC:9602): (prostaglandin I2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-5.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4	c.984A>C	p.Ser328Ser	synonymous_variant	Exon 3 of 3	ENST00000291294.7	NP_000951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIR	ENST00000291294.7	c.984A>C	p.Ser328Ser	synonymous_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1
PTGIR	ENST00000598865.5	c.348A>C	p.Ser116Ser	synonymous_variant	Exon 3 of 3	3		ENSP00000470799.1
PTGIR	ENST00000594275.1	c.255A>C	p.Ser85Ser	synonymous_variant	Exon 3 of 3	3		ENSP00000469408.1
PTGIR	ENST00000597185.1	c.171A>C	p.Ser57Ser	synonymous_variant	Exon 2 of 2	3		ENSP00000470566.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61325 AN: 151946 Hom.: 12455 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.399 AC: 99685 AN: 250078 Hom.: 20284 AF XY: 0.406 AC XY: 54969 AN XY: 135508

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.485

Gnomad EAS exome AF: 0.404

Gnomad SAS exome AF: 0.492

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.398

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.402 AC: 588278 AN: 1461664 Hom.: 119813 Cov.: 64 AF XY: 0.406 AC XY: 295234 AN XY: 727110

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.404 AC: 61413 AN: 152064 Hom.: 12484 Cov.: 33 AF XY: 0.402 AC XY: 29898 AN XY: 74318

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.440

Alfa AF: 0.382 Hom.: 4559

Bravo AF: 0.410

Asia WGS AF: 0.441 AC: 1534 AN: 3478

EpiCase AF: 0.410

EpiControl AF: 0.411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2229129; hg19: chr19-47124714; COSMIC: COSV52192172; COSMIC: COSV52192172;