rs3842801

Positions:

• chr9-122392160-T-C

Variant summary

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

The NM_000962.4(PTGS1):​c.1445-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,545,860 control chromosomes in the GnomAD database, including 2,690 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 0.077 (1394 hom., cov: 31)
  • Exomes 𝑓: 0.011 (1296 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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]

PTGS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1445-29T>C		intron_variant		ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.1445-29T>C		intron_variant		1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11688 AN: 152096 Hom.: 1387 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.0704

GnomAD3 exomes AF: 0.0249 AC: 5070 AN: 203752 Hom.: 500 AF XY: 0.0200 AC XY: 2168 AN XY: 108404

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0204

Gnomad EAS exome AF: 0.0000576

Gnomad SAS exome AF: 0.00713

Gnomad FIN exome AF: 0.000322

Gnomad NFE exome AF: 0.00379

Gnomad OTH exome AF: 0.0206

GnomAD4 exome AF: 0.0108 AC: 15041 AN: 1393646 Hom.: 1296 Cov.: 29 AF XY: 0.0101 AC XY: 6887 AN XY: 683902

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.0214

Gnomad4 ASJ exome AF: 0.0215

Gnomad4 EAS exome AF: 0.0000771

Gnomad4 SAS exome AF: 0.00756

Gnomad4 FIN exome AF: 0.000552

Gnomad4 NFE exome AF: 0.00262

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome AF: 0.0771 AC: 11737 AN: 152214 Hom.: 1394 Cov.: 31 AF XY: 0.0747 AC XY: 5562 AN XY: 74442

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0319

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0523 Hom.: 225

Bravo AF: 0.0862

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.52

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: rs3842801; hg19: chr9-125154439;