chr9-122388609-A-G

Variant names:

• chr9-122388609-A-G
• rs12551233
• NM_000962.4:c.1297-1589A>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.1297-1589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,172 control chromosomes in the GnomAD database, including 7,025 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 0.21 (7025 hom., cov: 32)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 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.1297-1589A>G		intron	N/A	NP_000953.2
	PTGS1	NM_080591.3		c.1186-1589A>G		intron	N/A	NP_542158.1
	PTGS1	NM_001271164.2		c.1153-1589A>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.1297-1589A>G		intron	N/A	ENSP00000354612.2
	PTGS1	ENST00000223423.8	TSL:1	c.1186-1589A>G		intron	N/A	ENSP00000223423.4
	PTGS1	ENST00000619306.5	TSL:5	c.1153-1589A>G		intron	N/A	ENSP00000483540.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31474 AN: 152054 Hom.: 6998 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.207 AC: 31557 AN: 152172 Hom.: 7025 Cov.: 32 AF XY: 0.202 AC XY: 15064 AN XY: 74406

African (AFR) AF: 0.557 AC: 23111 AN: 41458

American (AMR) AF: 0.110 AC: 1677 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.0594 AC: 308 AN: 5182

South Asian (SAS) AF: 0.152 AC: 734 AN: 4826

European-Finnish (FIN) AF: 0.0471 AC: 500 AN: 10614

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0640 AC: 4352 AN: 68010

Other (OTH) AF: 0.184 AC: 389 AN: 2114

Alfa AF: 0.105 Hom.: 3086

Bravo AF: 0.224

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		-0.57
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: rs12551233; hg19: chr9-125150888;