rs2302821

Positions:

• chr9-129739602-A-C
• chr9-129739602-A-G
• chr9-129739602-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004878.5(PTGES):​c.*9T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,548,682 control chromosomes in the GnomAD database, including 20,091 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 0.19 (4119 hom., cov: 32)
  • Exomes 𝑓: 0.11 (15972 hom.)
• Consequence: PTGES NM_004878.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES	NM_004878.5	c.*9T>G		3_prime_UTR_variant	3/3	ENST00000340607.5	NP_004869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGES	ENST00000340607.5	c.*9T>G		3_prime_UTR_variant	3/3	1	NM_004878.5	ENSP00000342385.4
PTGES	ENST00000481476.1	n.597T>G		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28369 AN: 152042 Hom.: 4110 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.171 AC: 26438 AN: 154458 Hom.: 3843 AF XY: 0.171 AC XY: 13963 AN XY: 81496

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.0451

Gnomad EAS exome AF: 0.552

Gnomad SAS exome AF: 0.255

Gnomad FIN exome AF: 0.0942

Gnomad NFE exome AF: 0.0774

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.112 AC: 157055 AN: 1396522 Hom.: 15972 Cov.: 31 AF XY: 0.115 AC XY: 79199 AN XY: 688608

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.0429

Gnomad4 EAS exome AF: 0.574

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.0792

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.187 AC: 28413 AN: 152160 Hom.: 4119 Cov.: 32 AF XY: 0.191 AC XY: 14216 AN XY: 74390

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0994 Hom.: 1839

Bravo AF: 0.199

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.092
DANN	Benign	0.49

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: rs2302821; hg19: chr9-132501881; COSMIC: COSV61393575;