rs4837404

Positions:

• chr9-129743380-G-A

Variant summary

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

The NM_004878.5(PTGES):​c.210-3520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,168 control chromosomes in the GnomAD database, including 42,004 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 0.73 (42004 hom., cov: 32)
• Consequence: PTGES NM_004878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGES	NM_004878.5	c.210-3520C>T		intron_variant		ENST00000340607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGES	ENST00000340607.5	c.210-3520C>T		intron_variant		1	NM_004878.5	P1
PTGES	ENST00000481476.1	n.339-3520C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111148 AN: 152050 Hom.: 41953 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.731 AC: 111255 AN: 152168 Hom.: 42004 Cov.: 32 AF XY: 0.731 AC XY: 54388 AN XY: 74378

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.734

Alfa AF: 0.655 Hom.: 33856

Bravo AF: 0.744

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.56

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: rs4837404; hg19: chr9-132505659;