rs9299280

Variant names:

• chr9-122385408-G-A
• rs9299280
• NM_000962.4:c.1010-1038G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000962.4(PTGS1):​c.1010-1038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,318 control chromosomes in the GnomAD database, including 9,210 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 0.27 (9210 hom., cov: 30)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1010-1038G>A		intron_variant	Intron 8 of 10	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.1010-1038G>A		intron_variant	Intron 8 of 10	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41459 AN: 151200 Hom.: 9166 Cov.: 30

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.275 AC: 41557 AN: 151318 Hom.: 9210 Cov.: 30 AF XY: 0.270 AC XY: 19948 AN XY: 73904

African (AFR) AF: 0.612 AC: 25161 AN: 41126

American (AMR) AF: 0.246 AC: 3721 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3464

East Asian (EAS) AF: 0.0450 AC: 232 AN: 5160

South Asian (SAS) AF: 0.0856 AC: 409 AN: 4778

European-Finnish (FIN) AF: 0.130 AC: 1356 AN: 10466

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9584 AN: 67878

Other (OTH) AF: 0.252 AC: 529 AN: 2098

Alfa AF: 0.254 Hom.: 1501

Bravo AF: 0.298

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.28
PhyloP100		0.16
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: rs9299280; hg19: chr9-125147687;