Genetic Variant NM_000960.4:c.984A>C (chr19-46621457-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.59

Publications

20 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.984A>C	p.Ser328Ser	synonymous_variant	Exon 3 of 3	ENST00000291294.7	NP_000951.1	P43119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIR	ENST00000291294.7 link	c.984A>C	p.Ser328Ser	synonymous_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1		P43119

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61325

AN:

151946

Hom.:

12455

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.399

AC:

99685

AN:

250078

AF XY:

0.406

show subpopulations

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 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.:

AF XY:

0.406

AC XY:

295234

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.431

AC:

14422

AN:

33468

American (AMR)

AF:

0.325

AC:

14537

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12665

AN:

26126

East Asian (EAS)

AF:

0.369

AC:

14643

AN:

39700

South Asian (SAS)

AF:

0.491

AC:

42345

AN:

86256

European-Finnish (FIN)

AF:

0.325

AC:

17334

AN:

53362

Middle Eastern (MID)

AF:

0.485

AC:

2796

AN:

5764

European-Non Finnish (NFE)

AF:

0.400

AC:

444560

AN:

1111884

Other (OTH)

AF:

0.414

AC:

24976

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

23554

47107

70661

94214

117768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13966

27932

41898

55864

69830

<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:

0.404

AC:

61413

AN:

152064

Hom.:

12484

Cov.:

AF XY:

0.402

AC XY:

29898

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.438

AC:

18151

AN:

41478

American (AMR)

AF:

0.368

AC:

5623

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1685

AN:

3472

East Asian (EAS)

AF:

0.398

AC:

2049

AN:

5152

South Asian (SAS)

AF:

0.483

AC:

2328

AN:

4820

European-Finnish (FIN)

AF:

0.311

AC:

3288

AN:

10570

Middle Eastern (MID)

AF:

0.510

AC:

148

AN:

290

European-Non Finnish (NFE)

AF:

0.396

AC:

26896

AN:

67966

Other (OTH)

AF:

0.440

AC:

929

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2006

4013

6019

8026

10032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.382

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

(source)

DANN

Benign

0.44

PhyloP100

-5.6

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