9-122378417-G-C

Position:

• chr9-122378417-G-C

Variant summary

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

The NM_000962.4(PTGS1):​c.212-16G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,612,248 control chromosomes in the GnomAD database, including 38,185 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 (8443 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29742 hom.)
• Consequence: PTGS1 NM_000962.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4	c.212-16G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7	c.212-16G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000962.4	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44116 AN: 152086 Hom.: 8410 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.217 AC: 54053 AN: 249032 Hom.: 7138 AF XY: 0.210 AC XY: 28374 AN XY: 134794

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.0987

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.191 AC: 278591 AN: 1460044 Hom.: 29742 Cov.: 34 AF XY: 0.192 AC XY: 139239 AN XY: 726422

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0889

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.290 AC: 44206 AN: 152204 Hom.: 8443 Cov.: 33 AF XY: 0.286 AC XY: 21267 AN XY: 74420

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.281

Alfa AF: 0.157 Hom.: 452

Bravo AF: 0.305

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.40

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: rs2282169; hg19: chr9-125140696;