chr9-122378047-G-A

Position:

• chr9-122378047-G-A

Variant summary

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

The ENST00000362012.7(PTGS1):​c.211+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,581,350 control chromosomes in the GnomAD database, including 290 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 0.025 (141 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (149 hom.)
• Consequence: PTGS1 ENST00000362012.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.211+32G>A		intron_variant		ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.211+32G>A		intron_variant		1	NM_000962.4	ENSP00000354612	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3799 AN: 152182 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00811 AC: 1993 AN: 245886 Hom.: 60 AF XY: 0.00646 AC XY: 860 AN XY: 133210

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00152

Gnomad SAS exome AF: 0.00223

Gnomad FIN exome AF: 0.000633

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.00560

GnomAD4 exome AF: 0.00556 AC: 7947 AN: 1429050 Hom.: 149 Cov.: 28 AF XY: 0.00511 AC XY: 3643 AN XY: 712902

Gnomad4 AFR exome AF: 0.0858

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00142

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.000792

Gnomad4 NFE exome AF: 0.00371

Gnomad4 OTH exome AF: 0.00812

GnomAD4 genome AF: 0.0250 AC: 3811 AN: 152300 Hom.: 141 Cov.: 33 AF XY: 0.0241 AC XY: 1798 AN XY: 74472

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00345

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0191 Hom.: 20

Bravo AF: 0.0280

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.55

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: rs876567; hg19: chr9-125140326;