rs10306163

Positions:

• chr9-122387691-A-G

Variant summary

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

The NM_000962.4(PTGS1):​c.1296+959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,110 control chromosomes in the GnomAD database, including 11,642 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 (11642 hom., cov: 32)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.1296+959A>G		intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.1296+959A>G		intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50238 AN: 151994 Hom.: 11593 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50351 AN: 152110 Hom.: 11642 Cov.: 32 AF XY: 0.326 AC XY: 24225 AN XY: 74362

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.318

Alfa AF: 0.220 Hom.: 5805

Bravo AF: 0.350

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.37

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: rs10306163; hg19: chr9-125149970;