Genetic Variant PTGS1:c.212-16G>C (chr9-122378417-G-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.212-16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,612,248 control chromosomes in the GnomAD database, including 38,185 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 0.29 ( 8443 hom., cov: 33)

Exomes 𝑓: 0.19 ( 29742 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.586

Publications

19 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.212-16G>C		intron_variant	Intron 3 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.212-16G>C		intron_variant	Intron 3 of 10	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44116

AN:

152086

Hom.:

8410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.217

AC:

54053

AN:

249032

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.545

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0987

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.191

AC:

278591

AN:

1460044

Hom.:

29742

Cov.:

AF XY:

0.192

AC XY:

139239

AN XY:

726422

show subpopulations

African (AFR)

AF:

0.553

AC:

18527

AN:

33480

American (AMR)

AF:

0.263

AC:

11751

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4636

AN:

26136

East Asian (EAS)

AF:

0.0889

AC:

3531

AN:

39700

South Asian (SAS)

AF:

0.240

AC:

20675

AN:

86254

European-Finnish (FIN)

AF:

0.158

AC:

8154

AN:

51676

Middle Eastern (MID)

AF:

0.221

AC:

1275

AN:

5768

European-Non Finnish (NFE)

AF:

0.178

AC:

197819

AN:

1111926

Other (OTH)

AF:

0.202

AC:

12223

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12368

24736

37104

49472

61840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7062

14124

21186

28248

35310

<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:

0.290

AC:

44206

AN:

152204

Hom.:

8443

Cov.:

AF XY:

0.286

AC XY:

21267

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.540

AC:

22419

AN:

41504

American (AMR)

AF:

0.283

AC:

4332

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

596

AN:

3472

East Asian (EAS)

AF:

0.103

AC:

536

AN:

5186

South Asian (SAS)

AF:

0.225

AC:

1087

AN:

4822

European-Finnish (FIN)

AF:

0.148

AC:

1570

AN:

10608

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12782

AN:

67992

Other (OTH)

AF:

0.281

AC:

593

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1448

2896

4343

5791

7239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.157

Hom.:

452

Bravo

AF:

0.305

Asia WGS

AF:

0.219

AC:

761

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.1

(source)

DANN

Benign

0.40

PhyloP100

0.59

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