9-122373210-T-C

Variant names:

• chr9-122373210-T-C
• rs10306122
• NM_000962.4:c.94+1938T>C

Variant summary

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

The NM_000962.4(PTGS1):​c.94+1938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,236 control chromosomes in the GnomAD database, including 743 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 0.071 (743 hom., cov: 32)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.94+1938T>C		intron_variant	Intron 2 of 10	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.94+1938T>C		intron_variant	Intron 2 of 10	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10823 AN: 152118 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0705

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0711 AC: 10826 AN: 152236 Hom.: 743 Cov.: 32 AF XY: 0.0746 AC XY: 5554 AN XY: 74444

African (AFR) AF: 0.0197 AC: 819 AN: 41538

American (AMR) AF: 0.0729 AC: 1115 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 228 AN: 3464

East Asian (EAS) AF: 0.384 AC: 1981 AN: 5164

South Asian (SAS) AF: 0.180 AC: 870 AN: 4826

European-Finnish (FIN) AF: 0.0705 AC: 749 AN: 10624

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0712 AC: 4841 AN: 68012

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0648 Hom.: 337

Bravo AF: 0.0680

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.72
PhyloP100		-0.0080
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: rs10306122; hg19: chr9-125135489;