dbSNP rs10306194: PTGS1:c.*2375C>A (chr9-122394919-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000962.4(PTGS1):c.*2375C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,308 control chromosomes in the GnomAD database, including 1,025 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 0.10 ( 1025 hom., cov: 32)

Exomes 𝑓: 0.096 ( 0 hom. )

Consequence

PTGS1
NM_000962.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 12
Inheritance: SD Classification: LIMITED Submitted by: ClinGen

PTGS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS1	NM_000962.4 link	c.*2375C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000362012.7	NP_000953.2	P23219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7 link	c.*2375C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15755

AN:

152136

Hom.:

1027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.0962

AC:

AN:

Hom.:

Cov.:

AF XY:

0.132

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.105

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.615

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15756

AN:

152256

Hom.:

1025

Cov.:

AF XY:

0.0989

AC XY:

7360

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0332

AC:

1379

AN:

41552

American (AMR)

AF:

0.130

AC:

1984

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

475

AN:

3470

East Asian (EAS)

AF:

0.0326

AC:

169

AN:

5184

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4828

European-Finnish (FIN)

AF:

0.0582

AC:

618

AN:

10618

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10140

AN:

68004

Other (OTH)

AF:

0.130

AC:

273

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

737

1474

2210

2947

3684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

2145

Bravo

AF:

0.105

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over