dbSNP rs3215925: PTGS1:c.762+14delA (chr9-122381760-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000962.4(PTGS1):c.762+14delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,609,406 control chromosomes in the GnomAD database, including 26,907 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 8622 hom., cov: 25)

Exomes 𝑓: 0.14 ( 18285 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.484

Publications

7 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.762+14delA		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.762+14delA		intron_variant	Intron 7 of 10	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40303

AN:

151880

Hom.:

8583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.163

AC:

40489

AN:

248618

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0472

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.136

AC:

198720

AN:

1457408

Hom.:

18285

Cov.:

AF XY:

0.134

AC XY:

97161

AN XY:

725176

show subpopulations

African (AFR)

AF:

0.607

AC:

20257

AN:

33358

American (AMR)

AF:

0.223

AC:

9950

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3264

AN:

26092

East Asian (EAS)

AF:

0.0367

AC:

1458

AN:

39678

South Asian (SAS)

AF:

0.0914

AC:

7858

AN:

85952

European-Finnish (FIN)

AF:

0.131

AC:

6984

AN:

53146

Middle Eastern (MID)

AF:

0.147

AC:

843

AN:

5750

European-Non Finnish (NFE)

AF:

0.125

AC:

139054

AN:

1108598

Other (OTH)

AF:

0.150

AC:

9052

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7920

15840

23759

31679

39599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5078

10156

15234

20312

25390

<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:

0.266

AC:

40397

AN:

151998

Hom.:

8622

Cov.:

AF XY:

0.261

AC XY:

19427

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.589

AC:

24381

AN:

41376

American (AMR)

AF:

0.241

AC:

3682

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3462

East Asian (EAS)

AF:

0.0445

AC:

230

AN:

5166

South Asian (SAS)

AF:

0.0865

AC:

417

AN:

4820

European-Finnish (FIN)

AF:

0.130

AC:

1378

AN:

10602

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9244

AN:

67976

Other (OTH)

AF:

0.241

AC:

509

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1178

2355

3533

4710

5888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.116

Hom.:

262

Bravo

AF:

0.286

Asia WGS

AF:

0.116

AC:

404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

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