Variant 9-122383532-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000962.4(PTGS1):c.786G>A(p.Pro262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,611,700 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 14 hom. )

Consequence

PTGS1
NM_000962.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.69

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-122383532-G-A is Benign according to our data. Variant chr9-122383532-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659481.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.69 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS1	NM_000962.4 linkuse as main transcript	c.786G>A	p.Pro262=	synonymous_variant	8/11	ENST00000362012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS1	ENST00000362012.7 linkuse as main transcript	c.786G>A	p.Pro262=	synonymous_variant	8/11	1	NM_000962.4	P1	P23219-1

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00293

AC:

731

AN:

249490

Hom.:

AF XY:

0.00287

AC XY:

388

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00241

AC:

3512

AN:

1459488

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

1664

AN XY:

725478

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000851

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00273

AC:

415

AN:

152212

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

264

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00106

EpiCase

AF:

0.00175

EpiControl

AF:

0.00178

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

May 01, 2022

PTGS1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over