Variant rs5794 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000962.4(PTGS1):c.1441G>A(p.Val481Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00799 in 1,613,992 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0082 ( 57 hom. )

Consequence

PTGS1
NM_000962.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.51

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:

PTGS1 (HGNC:):

PTGS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009871155).

BP6

Variant 9-122390342-G-A is Benign according to our data. Variant chr9-122390342-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024886.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4 linkuse as main transcript	c.1441G>A	p.Val481Ile	missense_variant	10/11	ENST00000362012.7	NP_000953.2	P23219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7 linkuse as main transcript	c.1441G>A	p.Val481Ile	missense_variant	10/11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

959

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00508

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00718

AC:

1798

AN:

250416

Hom.:

AF XY:

0.00736

AC XY:

996

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00554

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00646

Gnomad FIN exome

AF:

0.00607

Gnomad NFE exome

AF:

0.00944

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.00816

AC:

11931

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

5997

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.00584

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00760

Gnomad4 FIN exome

AF:

0.00743

Gnomad4 NFE exome

AF:

0.00877

Gnomad4 OTH exome

AF:

0.00715

GnomAD4 genome

AF:

0.00629

AC:

958

AN:

152354

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

480

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.00508

Gnomad4 NFE

AF:

0.00856

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00616

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00734

AC:

891

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00902

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PTGS1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;.;T;T;T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.87

D;D;.;D;D;D;D

MetaRNN

Benign

0.0099

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;N;N;.;.;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.92

.;N;.;N;.;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0040

.;D;.;D;.;D;D

Sift4G

Uncertain

0.010

.;D;.;D;.;D;D

Polyphen

0.10, 0.081

.;.;B;B;.;B;.

Vest4

0.23, 0.16, 0.23, 0.16

MVP

0.44

MPC

0.27

ClinPred

0.062

GERP RS

4.3

Varity_R

0.27

gMVP

0.63

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over