rs11792431

Positions:

• chr9-129752968-G-A
• chr9-129752968-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004878.5(PTGES):​c.45C>T​(p.Ala15=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES	NM_004878.5	c.45C>T	p.Ala15=	synonymous_variant	1/3	ENST00000340607.5	NP_004869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGES	ENST00000340607.5	c.45C>T	p.Ala15=	synonymous_variant	1/3	1	NM_004878.5	ENSP00000342385	P1
PTGES	ENST00000481476.1	n.52C>T		non_coding_transcript_exon_variant	1/4	1

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

GnomAD3 exomes AF: 0.0584 AC: 14454 AN: 247448 Hom.: 607 AF XY: 0.0575 AC XY: 7708 AN XY: 134154

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 SAS exome AF: 0.0452

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

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.0364

Gnomad4 EAS exome AF: 0.0221

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.0336

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.0628

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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0571

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0205

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0617 Hom.: 333

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs11792431; hg19: chr9-132515247;