Genetic Variant PTGIR:p.Thr373Thr (chr19-46621322-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000960.4(PTGIR):c.1119G>A(p.Thr373Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,521,222 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 40 hom. )

Consequence

PTGIR
NM_000960.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.20

Variant links:

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]

PTGIR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-46621322-C-T is Benign according to our data. Variant chr19-46621322-C-T is described in ClinVar as [Benign]. Clinvar id is 781491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2007/152346) while in subpopulation AFR AF= 0.0442 (1839/41578). AF 95% confidence interval is 0.0425. There are 49 homozygotes in gnomad4. There are 934 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4 link	c.1119G>A	p.Thr373Thr	synonymous_variant	Exon 3 of 3	ENST00000291294.7	NP_000951.1	P43119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTGIR	ENST00000291294.7 link	c.1119G>A	p.Thr373Thr	synonymous_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1	P43119
PTGIR	ENST00000598865.5 link	c.483G>A	p.Thr161Thr	synonymous_variant	Exon 3 of 3	3		ENSP00000470799.1	M0QZW0
PTGIR	ENST00000594275.1 link	c.390G>A	p.Thr130Thr	synonymous_variant	Exon 3 of 3	3		ENSP00000469408.1	M0QXV5
PTGIR	ENST00000597185.1 link	c.306G>A	p.Thr102Thr	synonymous_variant	Exon 2 of 2	3		ENSP00000470566.1	M0QZI2

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1994

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0440

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00450

AC:

816

AN:

181418

Hom.:

AF XY:

0.00348

AC XY:

333

AN XY:

95668

show subpopulations

Gnomad AFR exome

AF:

0.0474

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000260

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00337

GnomAD4 exome

AF:

0.00140

AC:

1922

AN:

1368876

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

855

AN XY:

670596

show subpopulations

Gnomad4 AFR exome

AF:

0.0453

Gnomad4 AMR exome

AF:

0.00337

Gnomad4 ASJ exome

AF:

0.00159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000506

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.00327

GnomAD4 genome

AF:

0.0132

AC:

2007

AN:

152346

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

934

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0442

Gnomad4 AMR

AF:

0.00764

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.50

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over