rs5788

chr9-122381513-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000962.4(PTGS1):c.639C>A(p.Gly213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,884 control chromosomes in the GnomAD database, including 27,432 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 0.27 (8808 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18624 hom.)
• Consequence: PTGS1 NM_000962.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

Genes affected

PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-0.377 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.639C>A	p.Gly213=	synonymous_variant	6/11	ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.639C>A	p.Gly213=	synonymous_variant	6/11	1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40644 AN: 151960 Hom.: 8768 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.245

GnomAD3 exomes AF: 0.165 AC: 41416 AN: 251428 Hom.: 5540 AF XY: 0.150 AC XY: 20423 AN XY: 135882

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0474

Gnomad SAS exome AF: 0.0928

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.137 AC: 200339 AN: 1461806 Hom.: 18624 Cov.: 33 AF XY: 0.135 AC XY: 97936 AN XY: 727206

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0368

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.268 AC: 40741 AN: 152078 Hom.: 8808 Cov.: 32 AF XY: 0.263 AC XY: 19575 AN XY: 74334

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0442

Gnomad4 SAS AF: 0.0868

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.243

Alfa AF: 0.169 Hom.: 4220

Bravo AF: 0.290

Asia WGS AF: 0.117 AC: 408 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	7.3
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5788; hg19: chr9-125143792; COSMIC: COSV56290751;