dbSNP rs3842798: PTGS1:c.763-45T>C (chr9-122383464-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000962.4(PTGS1):c.763-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,559,346 control chromosomes in the GnomAD database, including 44,284 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 0.33 ( 12019 hom., cov: 30)

Exomes 𝑓: 0.20 ( 32265 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.617

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.763-45T>C		intron_variant	Intron 7 of 10	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.763-45T>C		intron_variant	Intron 7 of 10	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50346

AN:

151740

Hom.:

11967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.306

GnomAD2 exomes

AF:

0.234

AC:

50563

AN:

216048

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0990

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.197

AC:

277389

AN:

1407486

Hom.:

32265

Cov.:

AF XY:

0.197

AC XY:

136251

AN XY:

691056

show subpopulations

African (AFR)

AF:

0.690

AC:

22472

AN:

32576

American (AMR)

AF:

0.272

AC:

11396

AN:

41868

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4070

AN:

22954

East Asian (EAS)

AF:

0.0896

AC:

3492

AN:

38980

South Asian (SAS)

AF:

0.234

AC:

18250

AN:

77884

European-Finnish (FIN)

AF:

0.183

AC:

9360

AN:

51280

Middle Eastern (MID)

AF:

0.232

AC:

1272

AN:

5482

European-Non Finnish (NFE)

AF:

0.181

AC:

194694

AN:

1078470

Other (OTH)

AF:

0.214

AC:

12383

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10076

20152

30229

40305

50381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7168

14336

21504

28672

35840

<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:

0.332

AC:

50462

AN:

151860

Hom.:

12019

Cov.:

AF XY:

0.327

AC XY:

24279

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.673

AC:

27843

AN:

41374

American (AMR)

AF:

0.296

AC:

4519

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

598

AN:

3466

East Asian (EAS)

AF:

0.103

AC:

530

AN:

5154

South Asian (SAS)

AF:

0.222

AC:

1068

AN:

4814

European-Finnish (FIN)

AF:

0.177

AC:

1865

AN:

10562

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13131

AN:

67920

Other (OTH)

AF:

0.305

AC:

639

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1339

2678

4018

5357

6696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.244

Hom.:

1575

Bravo

AF:

0.352

Asia WGS

AF:

0.226

AC:

788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.30

(source)

DANN

Benign

0.36

PhyloP100

-0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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