dbSNP rs10306135: PTGS1:c.95-2483A>T (chr9-122375416-A-T) – 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.95-2483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 985,268 control chromosomes in the GnomAD database, including 9,412 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 0.14 ( 1644 hom., cov: 32)

Exomes 𝑓: 0.14 ( 7768 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

Publications

21 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 (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.95-2483A>T		intron_variant	Intron 2 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.95-2483A>T		intron_variant	Intron 2 of 10	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21490

AN:

152070

Hom.:

1645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.136

AC:

113032

AN:

833080

Hom.:

7768

Cov.:

AF XY:

0.136

AC XY:

52334

AN XY:

384706

show subpopulations

African (AFR)

AF:

0.149

AC:

2359

AN:

15780

American (AMR)

AF:

0.118

AC:

116

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

711

AN:

5152

East Asian (EAS)

AF:

0.0121

AC:

AN:

3630

South Asian (SAS)

AF:

0.177

AC:

2907

AN:

16460

European-Finnish (FIN)

AF:

0.101

AC:

AN:

276

Middle Eastern (MID)

AF:

0.113

AC:

183

AN:

1622

European-Non Finnish (NFE)

AF:

0.135

AC:

103205

AN:

761886

Other (OTH)

AF:

0.127

AC:

3479

AN:

27290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5072

10144

15217

20289

25361

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:

0.141

AC:

21522

AN:

152188

Hom.:

1644

Cov.:

AF XY:

0.140

AC XY:

10409

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.147

AC:

6106

AN:

41528

American (AMR)

AF:

0.132

AC:

2015

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

486

AN:

3470

East Asian (EAS)

AF:

0.0172

AC:

AN:

5162

South Asian (SAS)

AF:

0.170

AC:

817

AN:

4820

European-Finnish (FIN)

AF:

0.132

AC:

1398

AN:

10592

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10104

AN:

67992

Other (OTH)

AF:

0.161

AC:

340

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

956

1911

2867

3822

4778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.162

Hom.:

257

Bravo

AF:

0.137

Asia WGS

AF:

0.118

AC:

413

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

5.8

(source)

DANN

Benign

0.83

PhyloP100

-0.17

PromoterAI

0.021

Neutral

(source)

Mutation Taster

=300/0

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