Variant rs3842803 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000962.4(PTGS1):c.1512T>C(p.Pro504=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,613,186 control chromosomes in the GnomAD database, including 2,789 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 0.078 ( 1411 hom., cov: 31)

Exomes 𝑓: 0.011 ( 1378 hom. )

Consequence

PTGS1
NM_000962.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.41

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=-5.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4 linkuse as main transcript	c.1512T>C	p.Pro504=	synonymous_variant	11/11	ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7 linkuse as main transcript	c.1512T>C	p.Pro504=	synonymous_variant	11/11	1	NM_000962.4	P1	P23219-1

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11763

AN:

152072

Hom.:

1404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.0240

AC:

6041

AN:

251354

Hom.:

593

AF XY:

0.0191

AC XY:

2589

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00788

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0111

AC:

16238

AN:

1460996

Hom.:

1378

Cov.:

AF XY:

0.0103

AC XY:

7493

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00787

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00270

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0776

AC:

11814

AN:

152190

Hom.:

1411

Cov.:

AF XY:

0.0754

AC XY:

5612

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0395

Hom.:

359

Bravo

AF:

0.0868

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0060

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over