rs2241270

Positions:

• chr9-129752610-C-T

Variant summary

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

The NM_004878.5(PTGES):​c.126+277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,286 control chromosomes in the GnomAD database, including 2,651 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 0.17 (2651 hom., cov: 33)
• Consequence: PTGES NM_004878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGES	NM_004878.5	c.126+277G>A		intron_variant		ENST00000340607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGES	ENST00000340607.5	c.126+277G>A		intron_variant		1	NM_004878.5	P1
PTGES	ENST00000481476.1	n.133+277G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25628 AN: 152168 Hom.: 2635 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25674 AN: 152286 Hom.: 2651 Cov.: 33 AF XY: 0.165 AC XY: 12318 AN XY: 74476

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.166

Alfa AF: 0.141 Hom.: 827

Bravo AF: 0.176

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.94

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: rs2241270; hg19: chr9-132514889;