rs10306135

chr9-122375416-A-T

Variant summary

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

The NM_000962.4(PTGS1):c.95-2483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 985,268 control chromosomes in the GnomAD database, including 9,412 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 0.14 (1644 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7768 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.95-2483A>T		intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.95-2483A>T		intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21490 AN: 152070 Hom.: 1645 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.136 AC: 113032 AN: 833080 Hom.: 7768 Cov.: 30 AF XY: 0.136 AC XY: 52334 AN XY: 384706

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0121

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.141 AC: 21522 AN: 152188 Hom.: 1644 Cov.: 32 AF XY: 0.140 AC XY: 10409 AN XY: 74404

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.161

Alfa AF: 0.162 Hom.: 257

Bravo AF: 0.137

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.8
Dann	Benign	0.83

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: rs10306135; hg19: chr9-125137695;