dbSNP rs3842801: PTGS1:c.1445-29T>C (chr9-122392160-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.1445-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,545,860 control chromosomes in the GnomAD database, including 2,690 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 0.077 ( 1394 hom., cov: 31)

Exomes 𝑓: 0.011 ( 1296 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.365

Publications

8 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, AD, AR 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTGS1	NM_000962.4	MANE Select	c.1445-29T>C	intron	N/A	NP_000953.2
PTGS1	NM_080591.3		c.1334-29T>C	intron	N/A	NP_542158.1	P23219-2
PTGS1	NM_001271164.2		c.1301-29T>C	intron	N/A	NP_001258093.1	A0A087X296

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.1445-29T>C	intron	N/A	ENSP00000354612.2	P23219-1
PTGS1	ENST00000223423.8	TSL:1	c.1334-29T>C	intron	N/A	ENSP00000223423.4	P23219-2
PTGS1	ENST00000863393.1		c.1499-29T>C	intron	N/A	ENSP00000533452.1

Frequencies

GnomAD3 genomes

AF:

0.0768

AC:

11688

AN:

152096

Hom.:

1387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.0704

GnomAD2 exomes

AF:

0.0249

AC:

5070

AN:

203752

AF XY:

0.0200

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.0000576

Gnomad FIN exome

AF:

0.000322

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0108

AC:

15041

AN:

1393646

Hom.:

1296

Cov.:

AF XY:

0.0101

AC XY:

6887

AN XY:

683902

show subpopulations

African (AFR)

AF:

0.272

AC:

8645

AN:

31726

American (AMR)

AF:

0.0214

AC:

829

AN:

38690

Ashkenazi Jewish (ASJ)

AF:

0.0215

AC:

477

AN:

22180

East Asian (EAS)

AF:

0.0000771

AC:

AN:

38892

South Asian (SAS)

AF:

0.00756

AC:

570

AN:

75410

European-Finnish (FIN)

AF:

0.000552

AC:

AN:

50734

Middle Eastern (MID)

AF:

0.0591

AC:

322

AN:

5452

European-Non Finnish (NFE)

AF:

0.00262

AC:

2815

AN:

1073190

Other (OTH)

AF:

0.0236

AC:

1352

AN:

57372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

635

1270

1905

2540

3175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.0771

AC:

11737

AN:

152214

Hom.:

1394

Cov.:

AF XY:

0.0747

AC XY:

5562

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.258

AC:

10700

AN:

41500

American (AMR)

AF:

0.0319

AC:

488

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00381

AC:

259

AN:

68016

Other (OTH)

AF:

0.0706

AC:

149

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

441

882

1322

1763

2204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0490

Hom.:

328

Bravo

AF:

0.0862

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.1

(source)

DANN

Benign

0.52

PhyloP100

-0.36

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over