9-122374605-A-G

Variant names:

• chr9-122374605-A-G
• rs1213266
• NM_000962.4:c.95-3294A>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.95-3294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,084 control chromosomes in the GnomAD database, including 51,006 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 0.80 (51006 hom., cov: 32)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	NM_000962.4	MANE Select	c.95-3294A>G		intron	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.95-3294A>G		intron	N/A	NP_542158.1
	PTGS1	NM_001271164.2		c.95-3294A>G		intron	N/A	NP_001258093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.95-3294A>G		intron	N/A	ENSP00000354612.2
	PTGS1	ENST00000223423.8	TSL:1	c.95-3294A>G		intron	N/A	ENSP00000223423.4
	PTGS1	ENST00000619306.5	TSL:5	c.95-3294A>G		intron	N/A	ENSP00000483540.2

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121162 AN: 151966 Hom.: 51010 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.797 AC: 121191 AN: 152084 Hom.: 51006 Cov.: 32 AF XY: 0.801 AC XY: 59537 AN XY: 74354

African (AFR) AF: 0.494 AC: 20449 AN: 41420

American (AMR) AF: 0.864 AC: 13203 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4866 AN: 5148

South Asian (SAS) AF: 0.844 AC: 4072 AN: 4826

European-Finnish (FIN) AF: 0.926 AC: 9825 AN: 10612

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62837 AN: 68004

Other (OTH) AF: 0.814 AC: 1718 AN: 2110

Alfa AF: 0.894 Hom.: 119947

Bravo AF: 0.782

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1213266; hg19: chr9-125136884;