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GeneBe

rs3842802

chr9-122392241-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000962.4(PTGS1):c.1497G>A(p.Ala499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,607,794 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 31)
Exomes 𝑓: 0.0025 ( 71 hom. )

Consequence

PTGS1
NM_000962.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.93
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-122392241-G-A is Benign according to our data. Variant chr9-122392241-G-A is described in ClinVar as [Benign]. Clinvar id is 775276.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.93 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTGS1NM_000962.4 linkuse as main transcriptc.1497G>A p.Ala499= synonymous_variant 11/11 ENST00000362012.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTGS1ENST00000362012.7 linkuse as main transcriptc.1497G>A p.Ala499= synonymous_variant 11/111 NM_000962.4 P1P23219-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0160
AC:
2437
AN:
152108
Hom.:
56
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0521
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00844
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00128
Gnomad OTH
AF:
0.0192
GnomAD3 exomes
AF:
0.00543
AC:
1363
AN:
250930
Hom.:
30
AF XY:
0.00443
AC XY:
601
AN XY:
135612
show subpopulations
Gnomad AFR exome
AF:
0.0556
Gnomad AMR exome
AF:
0.00649
Gnomad ASJ exome
AF:
0.00439
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.00122
Gnomad OTH exome
AF:
0.00653
GnomAD4 exome
AF:
0.00246
AC:
3574
AN:
1455568
Hom.:
71
Cov.:
31
AF XY:
0.00231
AC XY:
1666
AN XY:
722560
show subpopulations
Gnomad4 AFR exome
AF:
0.0533
Gnomad4 AMR exome
AF:
0.00682
Gnomad4 ASJ exome
AF:
0.00430
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000841
Gnomad4 OTH exome
AF:
0.00592
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0160
AC:
2440
AN:
152226
Hom.:
56
Cov.:
31
AF XY:
0.0151
AC XY:
1123
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0521
Gnomad4 AMR
AF:
0.00843
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00128
Gnomad4 OTH
AF:
0.0190
Alfa
AF:
0.0100
Hom.:
18
Bravo
AF:
0.0184
Asia WGS
AF:
0.00375
AC:
14
AN:
3478
EpiCase
AF:
0.00153
EpiControl
AF:
0.00160

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 28, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
5.2
Dann
Benign
0.35
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs3842802; hg19: chr9-125154520; COSMIC: COSV56290864; API