dbSNP rs5270: PTGS2:c.-114+117C>G (chr1-186680587-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000680451.1(PTGS2):c.-114+117C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 406,366 control chromosomes in the GnomAD database, including 47 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 0.012 ( 36 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 11 hom. )

Consequence

PTGS2
ENST00000680451.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

Publications

17 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:

PACERR (HGNC:50552): (PTGS2 antisense NFKB1 complex-mediated expression regulator RNA) This gene represents transcription of a long non-coding RNA produced in antisense to the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. This transcript interacts with NF-kB transcriptional regulators to promote expression of PTGS2. [provided by RefSeq, Feb 2015]

PACERR 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=-0.8).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1838/152250) while in subpopulation AFR AF = 0.0416 (1727/41548). AF 95% confidence interval is 0.0399. There are 36 homozygotes in GnomAd4. There are 874 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1838 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.-297C>G		upstream_gene	N/A	NP_000954.1	P35354
	PACERR	NR_125801.1		n.-67G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTGS2	ENST00000680451.1		c.-114+117C>G	intron	N/A	ENSP00000506242.1	P35354
PACERR	ENST00000608917.4	TSL:6	n.480G>C	non_coding_transcript_exon	Exon 1 of 1
PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.-297C>G	upstream_gene	N/A	ENSP00000356438.5	P35354

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00670

GnomAD4 exome

AF:

0.00262

AC:

667

AN:

254116

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

316

AN XY:

131674

show subpopulations

African (AFR)

AF:

0.0451

AC:

296

AN:

6570

American (AMR)

AF:

0.00238

AC:

AN:

8822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8940

East Asian (EAS)

AF:

0.0133

AC:

263

AN:

19718

South Asian (SAS)

AF:

0.000265

AC:

AN:

15096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19198

Middle Eastern (MID)

AF:

0.000779

AC:

AN:

1284

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

158604

Other (OTH)

AF:

0.00466

AC:

AN:

15884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0121

AC:

1838

AN:

152250

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

874

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0416

AC:

1727

AN:

41548

American (AMR)

AF:

0.00445

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00425

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00664

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00895

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.1

(source)

DANN

Benign

0.50

PhyloP100

0.30

PromoterAI

-0.24

Neutral

(source)

Splicing

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