9-129752968-G-A

Variant names:

• chr9-129752968-G-A
• rs11792431
• NM_004878.5:c.45C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004878.5(PTGES):​c.45C>T​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,610,762 control chromosomes in the GnomAD database, including 4,396 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 0.092 (893 hom., cov: 33)
  • Exomes 𝑓: 0.064 (3503 hom.)
• Consequence: PTGES NM_004878.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.348 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	NM_004878.5	MANE Select	c.45C>T	p.Ala15Ala	synonymous	Exon 1 of 3	NP_004869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	ENST00000340607.5	TSL:1 MANE Select	c.45C>T	p.Ala15Ala	synonymous	Exon 1 of 3	ENSP00000342385.4
	PTGES	ENST00000481476.1	TSL:1	n.52C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14039 AN: 152202 Hom.: 878 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0914

GnomAD2 exomes AF: 0.0584 AC: 14454 AN: 247448 AF XY: 0.0575

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.0330

Gnomad ASJ exome AF: 0.0367

Gnomad EAS exome AF: 0.0235

Gnomad FIN exome AF: 0.0379

Gnomad NFE exome AF: 0.0622

Gnomad OTH exome AF: 0.0617

GnomAD4 exome AF: 0.0645 AC: 94026 AN: 1458442 Hom.: 3503 Cov.: 32 AF XY: 0.0636 AC XY: 46150 AN XY: 725686

African (AFR) AF: 0.190 AC: 6376 AN: 33480

American (AMR) AF: 0.0365 AC: 1631 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 952 AN: 26136

East Asian (EAS) AF: 0.0221 AC: 877 AN: 39698

South Asian (SAS) AF: 0.0454 AC: 3912 AN: 86256

European-Finnish (FIN) AF: 0.0336 AC: 1682 AN: 50040

Middle Eastern (MID) AF: 0.0766 AC: 442 AN: 5768

European-Non Finnish (NFE) AF: 0.0669 AC: 74365 AN: 1111974

Other (OTH) AF: 0.0628 AC: 3789 AN: 60368

GnomAD4 genome AF: 0.0925 AC: 14084 AN: 152320 Hom.: 893 Cov.: 33 AF XY: 0.0905 AC XY: 6738 AN XY: 74474

African (AFR) AF: 0.186 AC: 7723 AN: 41560

American (AMR) AF: 0.0571 AC: 874 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5172

South Asian (SAS) AF: 0.0511 AC: 247 AN: 4832

European-Finnish (FIN) AF: 0.0371 AC: 394 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0645 AC: 4385 AN: 68032

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0777 Hom.: 907

Bravo AF: 0.0976

Asia WGS AF: 0.0430 AC: 152 AN: 3478

EpiCase AF: 0.0627

EpiControl AF: 0.0646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		0.35
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11792431; hg19: chr9-132515247;