rs10306194

Positions:

• chr9-122394919-C-A
• chr9-122394919-C-G

Variant summary

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

The NM_000962.4(PTGS1):​c.*2375C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,308 control chromosomes in the GnomAD database, including 1,025 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 0.10 (1025 hom., cov: 32)
  • Exomes 𝑓: 0.096 (0 hom.)
• Consequence: PTGS1 NM_000962.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.*2375C>A		3_prime_UTR_variant	11/11	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.*2375C>A		3_prime_UTR_variant	11/11	1	NM_000962.4	ENSP00000354612	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15755 AN: 152136 Hom.: 1027 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0962 AC: 5 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.132 AC XY: 5 AN XY: 38

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.103 AC: 15756 AN: 152256 Hom.: 1025 Cov.: 32 AF XY: 0.0989 AC XY: 7360 AN XY: 74454

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.130

Alfa AF: 0.139 Hom.: 1553

Bravo AF: 0.105

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.72

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: rs10306194; hg19: chr9-125157198;