19-46621504-C-T

Variant names:

• chr19-46621504-C-T
• rs200650026
• NM_000960.4:c.937G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000960.4(PTGIR):​c.937G>A​(p.Gly313Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PTGIR NM_000960.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.366

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037818193).
• BP6: Variant 19-46621504-C-T is Benign according to our data. Variant chr19-46621504-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3220778.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4	c.937G>A	p.Gly313Arg	missense_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.937G>A	p.Gly313Arg	missense_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1
PTGIR	ENST00000598865.5	c.301G>A	p.Gly101Arg	missense_variant	Exon 3 of 3	3		ENSP00000470799.1
PTGIR	ENST00000594275.1	c.208G>A	p.Gly70Arg	missense_variant	Exon 3 of 3	3		ENSP00000469408.1
PTGIR	ENST00000597185.1	c.124G>A	p.Gly42Arg	missense_variant	Exon 2 of 2	3		ENSP00000470566.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000797 AC: 20 AN: 250878 Hom.: 0 AF XY: 0.0000884 AC XY: 12 AN XY: 135806

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000369 AC: 54 AN: 1461852 Hom.: 0 Cov.: 33 AF XY: 0.0000344 AC XY: 25 AN XY: 727226

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74464

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.79
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.038	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.46	N;.;.;.
REVEL	Benign	0.046
Sift	Benign	0.90	T;.;.;.
Sift4G	Benign	0.76	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.10
MutPred		0.50		Gain of MoRF binding (P = 0.0589);.;.;.;
MVP		0.16
MPC		0.20
ClinPred		0.0095	T
GERP RS		-2.3
Varity_R		0.028
gMVP		0.37

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: rs200650026; hg19: chr19-47124761;