rs3842787

Positions:

• chr9-122371228-C-T

Variant summary

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

The NM_001271368.2(PTGS1):​c.-248C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 1,607,982 control chromosomes in the GnomAD database, including 4,287 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 0.082 (637 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3650 hom.)
• Consequence: PTGS1 NM_001271368.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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]

PTGS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016974807).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4	c.50C>T	p.Pro17Leu	missense_variant	2/11	ENST00000362012.7	NP_000953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7	c.50C>T	p.Pro17Leu	missense_variant	2/11	1	NM_000962.4	ENSP00000354612.2

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12488 AN: 152226 Hom.: 635 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0649

GnomAD3 exomes AF: 0.0588 AC: 14508 AN: 246842 Hom.: 641 AF XY: 0.0558 AC XY: 7472 AN XY: 133852

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0137

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.0674

Gnomad OTH exome AF: 0.0507

GnomAD4 exome AF: 0.0657 AC: 95581 AN: 1455638 Hom.: 3650 Cov.: 38 AF XY: 0.0636 AC XY: 46101 AN XY: 724406

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0276

Gnomad4 ASJ exome AF: 0.0739

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0689

Gnomad4 OTH exome AF: 0.0635

GnomAD4 genome AF: 0.0820 AC: 12492 AN: 152344 Hom.: 637 Cov.: 33 AF XY: 0.0822 AC XY: 6125 AN XY: 74500

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0667 Hom.: 624

Bravo AF: 0.0778

TwinsUK AF: 0.0674 AC: 250

ALSPAC AF: 0.0669 AC: 258

ESP6500AA AF: 0.138 AC: 608

ESP6500EA AF: 0.0681 AC: 586

ExAC AF: 0.0606 AC: 7354

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0599

EpiControl AF: 0.0611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.086
DANN	Benign	0.79
DEOGEN2	Benign	0.073	T;T;T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.48	.;T;T;T;T
MetaRNN	Benign	0.0017	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.;.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.3	.;N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.49	.;T;.;D;T
Sift4G	Benign	0.32	T;T;.;.;T
Polyphen		0.33	B;B;.;.;P
Vest4		0.14
MPC		0.28
ClinPred		0.0026	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.019
gMVP		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: rs3842787; hg19: chr9-125133507; COSMIC: COSV56291601; COSMIC: COSV56291601;