rs10306155

Variant names:

• chr9-122384199-C-T
• rs10306155
• NM_000962.4:c.1009+444C>T

Variant summary

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

The NM_000962.4(PTGS1):​c.1009+444C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,078 control chromosomes in the GnomAD database, including 1,019 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 0.10 (1019 hom., cov: 31)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1009+444C>T		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.1009+444C>T		intron_variant	Intron 8 of 10	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15592 AN: 151960 Hom.: 1019 Cov.: 31

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.103 AC: 15596 AN: 152078 Hom.: 1019 Cov.: 31 AF XY: 0.103 AC XY: 7622 AN XY: 74332

African (AFR) AF: 0.0509 AC: 2114 AN: 41492

American (AMR) AF: 0.122 AC: 1868 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 334 AN: 3464

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5166

South Asian (SAS) AF: 0.0729 AC: 351 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1366 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9225 AN: 68000

Other (OTH) AF: 0.102 AC: 216 AN: 2110

Alfa AF: 0.105 Hom.: 507

Bravo AF: 0.0957

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.083
Mutation Taster		=99/1	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: rs10306155; hg19: chr9-125146478;