chr9-122383832-G-A

Position:

• chr9-122383832-G-A

Variant summary

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

The NM_000962.4(PTGS1):​c.1009+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,554,316 control chromosomes in the GnomAD database, including 2,341 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 (1241 hom., cov: 31)
  • Exomes 𝑓: 0.0080 (1100 hom.)
• Consequence: PTGS1 NM_000962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.1009+77G>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.1009+77G>A		intron_variant		1	NM_000962.4	ENSP00000354612	P1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10808 AN: 152046 Hom.: 1233 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.00802 AC: 11243 AN: 1402152 Hom.: 1100 AF XY: 0.00691 AC XY: 4774 AN XY: 690694

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.000708

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000753

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0713 AC: 10846 AN: 152164 Hom.: 1241 Cov.: 31 AF XY: 0.0692 AC XY: 5152 AN XY: 74416

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0621 Hom.: 144

Bravo AF: 0.0824

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
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: rs10306153; hg19: chr9-125146111; COSMIC: COSV56290241; COSMIC: COSV56290241;