Genetic Variant PTGS1:c.211+32G>A (chr9-122378047-G-A) – 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.211+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,581,350 control chromosomes in the GnomAD database, including 290 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 0.025 ( 141 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 149 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.94

Publications

3 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 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.211+32G>A	intron	N/A	NP_000953.2
PTGS1	NM_080591.3		c.211+32G>A	intron	N/A	NP_542158.1	P23219-2
PTGS1	NM_001271164.2		c.211+32G>A	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.211+32G>A	intron	N/A	ENSP00000354612.2	P23219-1
PTGS1	ENST00000223423.8	TSL:1	c.211+32G>A	intron	N/A	ENSP00000223423.4	P23219-2
PTGS1	ENST00000863393.1		c.211+32G>A	intron	N/A	ENSP00000533452.1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3799

AN:

152182

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.00811

AC:

1993

AN:

245886

AF XY:

0.00646

show subpopulations

Gnomad AFR exome

AF:

0.0804

Gnomad AMR exome

AF:

0.00574

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.000633

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.00560

GnomAD4 exome

AF:

0.00556

AC:

7947

AN:

1429050

Hom.:

149

Cov.:

AF XY:

0.00511

AC XY:

3643

AN XY:

712902

show subpopulations

African (AFR)

AF:

0.0858

AC:

2809

AN:

32752

American (AMR)

AF:

0.00574

AC:

256

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00139

AC:

AN:

25928

East Asian (EAS)

AF:

0.00142

AC:

AN:

39576

South Asian (SAS)

AF:

0.00204

AC:

175

AN:

85674

European-Finnish (FIN)

AF:

0.000792

AC:

AN:

47968

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00371

AC:

4031

AN:

1087334

Other (OTH)

AF:

0.00812

AC:

483

AN:

59496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

384

768

1153

1537

1921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0250

AC:

3811

AN:

152300

Hom.:

141

Cov.:

AF XY:

0.0241

AC XY:

1798

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0805

AC:

3343

AN:

41552

American (AMR)

AF:

0.0101

AC:

155

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00345

AC:

235

AN:

68028

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

172

345

517

690

862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0164

Hom.:

Bravo

AF:

0.0280

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.58

(source)

DANN

Benign

0.55

PhyloP100

-2.9

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