dbSNP rs3842803: PTGS1:p.Pro504Pro (chr9-122392256-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_000962.4(PTGS1):c.1512T>C(p.Pro504Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,613,186 control chromosomes in the GnomAD database, including 2,789 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 0.078 ( 1411 hom., cov: 31)

Exomes 𝑓: 0.011 ( 1378 hom. )

Consequence

PTGS1
NM_000962.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.41

Publications

11 publications found

Variant links:

Genes affected

PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

PTGS1 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 12
Inheritance: SD Classification: LIMITED Submitted by: ClinGen

PTGS1 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=-0.97).

BP7

Synonymous conserved (PhyloP=-5.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.1512T>C	p.Pro504Pro	synonymous_variant	Exon 11 of 11	ENST00000362012.7	NP_000953.2	P23219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7 link	c.1512T>C	p.Pro504Pro	synonymous_variant	Exon 11 of 11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11763

AN:

152072

Hom.:

1404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.0718

GnomAD2 exomes

AF:

0.0240

AC:

6041

AN:

251354

AF XY:

0.0191

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0111

AC:

16238

AN:

1460996

Hom.:

1378

Cov.:

AF XY:

0.0103

AC XY:

7493

AN XY:

726602

show subpopulations

African (AFR)

AF:

0.274

AC:

9182

AN:

33452

American (AMR)

AF:

0.0216

AC:

964

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0215

AC:

562

AN:

26124

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39648

South Asian (SAS)

AF:

0.00787

AC:

679

AN:

86234

European-Finnish (FIN)

AF:

0.000655

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.0600

AC:

346

AN:

5764

European-Non Finnish (NFE)

AF:

0.00270

AC:

2999

AN:

1111294

Other (OTH)

AF:

0.0243

AC:

1468

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

779

1557

2336

3114

3893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.0776

AC:

11814

AN:

152190

Hom.:

1411

Cov.:

AF XY:

0.0754

AC XY:

5612

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.260

AC:

10777

AN:

41480

American (AMR)

AF:

0.0317

AC:

485

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.00622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000470

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00379

AC:

258

AN:

68002

Other (OTH)

AF:

0.0720

AC:

152

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

444

887

1331

1774

2218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0416

Hom.:

379

Bravo

AF:

0.0868

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0060

(source)

DANN

Benign

0.30

PhyloP100

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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