Genetic Variant PTGS2:n.3286T>C (chr1-186673297-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000490885.6(PTGS2):n.3286T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,298 control chromosomes in the GnomAD database, including 69,377 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 0.95 ( 69377 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

PTGS2
ENST00000490885.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

55 publications found

Variant links:

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

PTGS2 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490885.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.*1056T>C		3_prime_UTR	Exon 10 of 10	NP_000954.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTGS2	ENST00000490885.6	TSL:1	n.3286T>C	non_coding_transcript_exon	Exon 9 of 9
PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.*1056T>C	3_prime_UTR	Exon 10 of 10	ENSP00000356438.5
PTGS2	ENST00000681605.1		n.*2543T>C	non_coding_transcript_exon	Exon 10 of 10	ENSP00000504900.1

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145218

AN:

152178

Hom.:

69318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.990

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.954

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.931

Gnomad FIN

AF:

0.922

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.944

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.954

AC:

145335

AN:

152296

Hom.:

69377

Cov.:

AF XY:

0.952

AC XY:

70868

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.990

AC:

41152

AN:

41578

American (AMR)

AF:

0.955

AC:

14612

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.905

AC:

3139

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5183

AN:

5188

South Asian (SAS)

AF:

0.930

AC:

4488

AN:

4826

European-Finnish (FIN)

AF:

0.922

AC:

9783

AN:

10614

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.939

AC:

63875

AN:

67992

Other (OTH)

AF:

0.944

AC:

1995

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

345

689

1034

1378

1723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.940

Hom.:

116523

Bravo

AF:

0.959

Asia WGS

AF:

0.967

AC:

3357

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

(source)

DANN

Benign

0.37

PhyloP100

-1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over