rs3842798

Positions:

• chr9-122383464-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.763-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,559,346 control chromosomes in the GnomAD database, including 44,284 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 0.33 (12019 hom., cov: 30)
  • Exomes 𝑓: 0.20 (32265 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.763-45T>C		intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.763-45T>C		intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50346 AN: 151740 Hom.: 11967 Cov.: 30

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.234 AC: 50563 AN: 216048 Hom.: 7916 AF XY: 0.223 AC XY: 25627 AN XY: 114726

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.0990

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.197 AC: 277389 AN: 1407486 Hom.: 32265 Cov.: 32 AF XY: 0.197 AC XY: 136251 AN XY: 691056

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0896

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.332 AC: 50462 AN: 151860 Hom.: 12019 Cov.: 30 AF XY: 0.327 AC XY: 24279 AN XY: 74218

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.305

Alfa AF: 0.244 Hom.: 1575

Bravo AF: 0.352

Asia WGS AF: 0.226 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3842798; hg19: chr9-125145743; COSMIC: COSV56292484;