rs3215925

Positions:

• chr9-122381760-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000962.4(PTGS1):​c.762+14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,609,406 control chromosomes in the GnomAD database, including 26,907 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (8622 hom., cov: 25)
  • Exomes 𝑓: 0.14 (18285 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.762+14del		intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.762+14del		intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40303 AN: 151880 Hom.: 8583 Cov.: 25

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.163 AC: 40489 AN: 248618 Hom.: 5249 AF XY: 0.149 AC XY: 19994 AN XY: 134462

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0472

Gnomad SAS exome AF: 0.0924

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.136 AC: 198720 AN: 1457408 Hom.: 18285 Cov.: 30 AF XY: 0.134 AC XY: 97161 AN XY: 725176

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0367

Gnomad4 SAS exome AF: 0.0914

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.266 AC: 40397 AN: 151998 Hom.: 8622 Cov.: 25 AF XY: 0.261 AC XY: 19427 AN XY: 74326

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0445

Gnomad4 SAS AF: 0.0865

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.241

Alfa AF: 0.116 Hom.: 262

Bravo AF: 0.286

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3215925; hg19: chr9-125144039; COSMIC: COSV56290196;