chr9-122383340-G-A

Variant names:

• chr9-122383340-G-A
• rs4240474
• NM_000962.4:c.763-169G>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.763-169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,452 control chromosomes in the GnomAD database, including 8,603 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 (8603 hom., cov: 29)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.763-169G>A		intron_variant	Intron 7 of 10	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.763-169G>A		intron_variant	Intron 7 of 10	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40162 AN: 151336 Hom.: 8565 Cov.: 29

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0916

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.0862

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.266 AC: 40254 AN: 151452 Hom.: 8603 Cov.: 29 AF XY: 0.261 AC XY: 19352 AN XY: 74022

African (AFR) AF: 0.589 AC: 24230 AN: 41112

American (AMR) AF: 0.244 AC: 3713 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3466

East Asian (EAS) AF: 0.0446 AC: 230 AN: 5156

South Asian (SAS) AF: 0.0858 AC: 412 AN: 4800

European-Finnish (FIN) AF: 0.131 AC: 1374 AN: 10526

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9234 AN: 67860

Other (OTH) AF: 0.241 AC: 504 AN: 2094

Alfa AF: 0.236 Hom.: 1014

Bravo AF: 0.289

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	-0.83
CADD	Benign	10
DANN	Benign	0.43
PhyloP100		0.60
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: rs4240474; hg19: chr9-125145619;