rs4273915

Positions:

• chr9-122383050-G-C
• chr9-122383050-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000362012.7(PTGS1):​c.763-459G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,998 control chromosomes in the GnomAD database, including 9,426 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 0.29 (9426 hom., cov: 32)
• Consequence: PTGS1 ENST00000362012.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.763-459G>C		intron_variant		ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.763-459G>C		intron_variant		1	NM_000962.4	ENSP00000354612	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44456 AN: 151880 Hom.: 9389 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.293 AC: 44557 AN: 151998 Hom.: 9426 Cov.: 32 AF XY: 0.289 AC XY: 21466 AN XY: 74306

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0674

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.272

Alfa AF: 0.251 Hom.: 776

Bravo AF: 0.312

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs4273915; hg19: chr9-125145329;