Genetic Variant PTGS2:c.970+111T>C (chr1-186676356-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 NM_000963.4(PTGS2):c.970+111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,437,498 control chromosomes in the GnomAD database, including 11,827 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 0.12 ( 1253 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10574 hom. )

Consequence

PTGS2
NM_000963.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

22 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000963.4. 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.970+111T>C		intron	N/A	NP_000954.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.970+111T>C	intron	N/A	ENSP00000356438.5
PTGS2	ENST00000490885.6	TSL:1	n.1214T>C	non_coding_transcript_exon	Exon 7 of 9
PTGS2	ENST00000559627.1	TSL:1	n.*368+111T>C	intron	N/A	ENSP00000454130.1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18889

AN:

152158

Hom.:

1244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.0419

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0678

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.125

AC:

160052

AN:

1285224

Hom.:

10574

Cov.:

AF XY:

0.125

AC XY:

79841

AN XY:

637686

show subpopulations

African (AFR)

AF:

0.127

AC:

3698

AN:

29028

American (AMR)

AF:

0.158

AC:

5508

AN:

34814

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

4229

AN:

20630

East Asian (EAS)

AF:

0.0306

AC:

1185

AN:

38708

South Asian (SAS)

AF:

0.131

AC:

9257

AN:

70656

European-Finnish (FIN)

AF:

0.0776

AC:

3564

AN:

45908

Middle Eastern (MID)

AF:

0.171

AC:

884

AN:

5166

European-Non Finnish (NFE)

AF:

0.126

AC:

124661

AN:

986348

Other (OTH)

AF:

0.131

AC:

7066

AN:

53966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

7110

14220

21329

28439

35549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4408

8816

13224

17632

22040

<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:

0.124

AC:

18918

AN:

152274

Hom.:

1253

Cov.:

AF XY:

0.121

AC XY:

9000

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.128

AC:

5331

AN:

41544

American (AMR)

AF:

0.137

AC:

2098

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3472

East Asian (EAS)

AF:

0.0416

AC:

216

AN:

5188

South Asian (SAS)

AF:

0.133

AC:

644

AN:

4826

European-Finnish (FIN)

AF:

0.0678

AC:

719

AN:

10610

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8807

AN:

68018

Other (OTH)

AF:

0.145

AC:

307

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

852

1704

2557

3409

4261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.124

Hom.:

2010

Bravo

AF:

0.130

Asia WGS

AF:

0.126

AC:

438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.97

(source)

DANN

Benign

0.51

PhyloP100

0.038

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