Genetic Variant PTGIR:c.*754T>C (chr19-46620526-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000960.4(PTGIR):c.*754T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 985,036 control chromosomes in the GnomAD database, including 61,628 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 0.31 ( 7563 hom., cov: 31)

Exomes 𝑓: 0.36 ( 54065 hom. )

Consequence

PTGIR
NM_000960.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.664

Publications

61 publications found

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:

ENSG00000302712 (HGNC:):

ENSG00000302712 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4 link	c.*754T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000291294.7	NP_000951.1	P43119

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTGIR	ENST00000291294.7 link	c.*754T>C	3_prime_UTR_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1	P43119
PTGIR	ENST00000718329.1 link	c.769-1198T>C	intron_variant	Intron 2 of 2			ENSP00000520766.1
ENSG00000302712	ENST00000789035.1 link	n.288-595A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46902

AN:

151732

Hom.:

7563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.0854

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.359

AC:

299168

AN:

833186

Hom.:

54065

Cov.:

AF XY:

0.361

AC XY:

138762

AN XY:

384776

show subpopulations

African (AFR)

AF:

0.269

AC:

4239

AN:

15780

American (AMR)

AF:

0.211

AC:

208

AN:

986

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

2338

AN:

5152

East Asian (EAS)

AF:

0.0959

AC:

348

AN:

3630

South Asian (SAS)

AF:

0.392

AC:

6445

AN:

16460

European-Finnish (FIN)

AF:

0.276

AC:

AN:

290

Middle Eastern (MID)

AF:

0.408

AC:

663

AN:

1624

European-Non Finnish (NFE)

AF:

0.361

AC:

275297

AN:

761950

Other (OTH)

AF:

0.350

AC:

9550

AN:

27314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

12029

24058

36087

48116

60145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12022

24044

36066

48088

60110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.309

AC:

46928

AN:

151850

Hom.:

7563

Cov.:

AF XY:

0.303

AC XY:

22483

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.277

AC:

11452

AN:

41352

American (AMR)

AF:

0.241

AC:

3684

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1604

AN:

3472

East Asian (EAS)

AF:

0.0854

AC:

441

AN:

5166

South Asian (SAS)

AF:

0.370

AC:

1779

AN:

4812

European-Finnish (FIN)

AF:

0.248

AC:

2615

AN:

10542

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.356

AC:

24206

AN:

67946

Other (OTH)

AF:

0.338

AC:

711

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1599

3198

4796

6395

7994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.336

Hom.:

17316

Bravo

AF:

0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.94

(source)

DANN

Benign

0.62

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over