dbSNP rs5788: PTGS1:p.Gly213Gly (chr9-122381513-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000962.4(PTGS1):c.639C>A(p.Gly213Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,884 control chromosomes in the GnomAD database, including 27,432 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 0.27 ( 8808 hom., cov: 32)

Exomes 𝑓: 0.14 ( 18624 hom. )

Consequence

PTGS1
NM_000962.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.377

Publications

56 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP7

Synonymous conserved (PhyloP=-0.377 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.639C>A	p.Gly213Gly	synonymous_variant	Exon 6 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.639C>A	p.Gly213Gly	synonymous_variant	Exon 6 of 11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40644

AN:

151960

Hom.:

8768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0441

Gnomad SAS

AF:

0.0871

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.245

GnomAD2 exomes

AF:

0.165

AC:

41416

AN:

251428

AF XY:

0.150

show subpopulations

Gnomad AFR exome

AF:

0.611

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0474

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.137

AC:

200339

AN:

1461806

Hom.:

18624

Cov.:

AF XY:

0.135

AC XY:

97936

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.616

AC:

20609

AN:

33472

American (AMR)

AF:

0.224

AC:

10037

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3276

AN:

26136

East Asian (EAS)

AF:

0.0368

AC:

1461

AN:

39700

South Asian (SAS)

AF:

0.0918

AC:

7916

AN:

86252

European-Finnish (FIN)

AF:

0.132

AC:

7045

AN:

53420

Middle Eastern (MID)

AF:

0.148

AC:

854

AN:

5768

European-Non Finnish (NFE)

AF:

0.126

AC:

140000

AN:

1111942

Other (OTH)

AF:

0.151

AC:

9141

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10149

20298

30446

40595

50744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5124

10248

15372

20496

25620

<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:

0.268

AC:

40741

AN:

152078

Hom.:

8808

Cov.:

AF XY:

0.263

AC XY:

19575

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.596

AC:

24695

AN:

41438

American (AMR)

AF:

0.241

AC:

3691

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

423

AN:

3470

East Asian (EAS)

AF:

0.0442

AC:

229

AN:

5180

South Asian (SAS)

AF:

0.0868

AC:

418

AN:

4818

European-Finnish (FIN)

AF:

0.131

AC:

1383

AN:

10584

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9253

AN:

67984

Other (OTH)

AF:

0.243

AC:

513

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1193

2386

3579

4772

5965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.210

Hom.:

9992

Bravo

AF:

0.290

Asia WGS

AF:

0.117

AC:

408

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

7.3

(source)

DANN

Benign

0.74

PhyloP100

-0.38

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

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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