dbSNP rs45499692: PTGES:p.Val7Glu (chr9-129752993-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004878.5(PTGES):c.20T>A(p.Val7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,607,706 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 20 hom., cov: 33)

Exomes 𝑓: 0.00065 ( 4 hom. )

Consequence

PTGES
NM_004878.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00800

Publications

4 publications found

Variant links:

Genes affected

PTGES (HGNC:9599): (prostaglandin E synthase) The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53 induced apoptosis. Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses. [provided by RefSeq, Jul 2008]

PTGES links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030754805).

BP6

Variant 9-129752993-A-T is Benign according to our data. Variant chr9-129752993-A-T is described in ClinVar as Benign. ClinVar VariationId is 719466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00651 (992/152342) while in subpopulation AFR AF = 0.0226 (941/41576). AF 95% confidence interval is 0.0214. There are 20 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004878.5. 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
	PTGES	NM_004878.5	MANE Select	c.20T>A	p.Val7Glu	missense	Exon 1 of 3	NP_004869.1	O14684

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	ENST00000340607.5	TSL:1 MANE Select	c.20T>A	p.Val7Glu	missense	Exon 1 of 3	ENSP00000342385.4	O14684
	PTGES	ENST00000481476.1	TSL:1	n.27T>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

989

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00165

AC:

404

AN:

245070

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

AF:

0.000646

AC:

940

AN:

1455364

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

414

AN XY:

724280

show subpopulations

African (AFR)

AF:

0.0222

AC:

742

AN:

33480

American (AMR)

AF:

0.00101

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47134

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000746

AC:

AN:

1111882

Other (OTH)

AF:

0.00106

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00651

AC:

992

AN:

152342

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0226

AC:

941

AN:

41576

American (AMR)

AF:

0.00222

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68034

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

142

189

236

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:

0.00119

Hom.:

Bravo

AF:

0.00705

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00201

AC:

244

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

-0.0080

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

REVEL

Benign

0.026

Sift

Benign

0.047

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.071

MVP

0.043

MPC

0.82

ClinPred

0.0049

GERP RS

-3.7

PromoterAI

0.13

Neutral

(source)

Varity_R

0.26

gMVP

0.45

Mutation Taster

=97/3

polymorphism

(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