chr9-122387691-A-G

Variant names:

• chr9-122387691-A-G
• rs10306163
• NM_000962.4:c.1296+959A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 12

  Inheritance: SD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1296+959A>G		intron_variant	Intron 9 of 10	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.1296+959A>G		intron_variant	Intron 9 of 10	1	NM_000962.4	ENSP00000354612.2

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

African (AFR) AF: 0.653 AC: 27081 AN: 41464

American (AMR) AF: 0.296 AC: 4520 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3470

East Asian (EAS) AF: 0.104 AC: 540 AN: 5182

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1864 AN: 10598

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13629 AN: 67974

Other (OTH) AF: 0.318 AC: 672 AN: 2112

Alfa AF: 0.237 Hom.: 9929

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
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10306163; hg19: chr9-125149970;