Variant 9-122381757-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000962.4(PTGS1):c.762+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,596,538 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 107 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 81 hom. )

Consequence

PTGS1
NM_000962.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.947

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 9-122381757-G-A is Benign according to our data. Variant chr9-122381757-G-A is described in ClinVar as [Benign]. Clinvar id is 792137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4 linkuse as main transcript	c.762+10G>A		intron_variant		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.762+10G>A		intron_variant		1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3041

AN:

137274

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0967

Gnomad AMI

AF:

0.00556

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.000585

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000406

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00539

AC:

1279

AN:

237242

Hom.:

AF XY:

0.00391

AC XY:

505

AN XY:

129096

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.000306

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00209

AC:

3054

AN:

1459208

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1324

AN XY:

726008

show subpopulations

Gnomad4 AFR exome

AF:

0.0709

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.00461

GnomAD4 genome

AF:

0.0222

AC:

3049

AN:

137330

Hom.:

107

Cov.:

AF XY:

0.0214

AC XY:

1444

AN XY:

67334

show subpopulations

Gnomad4 AFR

AF:

0.0967

Gnomad4 AMR

AF:

0.00792

Gnomad4 ASJ

AF:

0.000585

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00127

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000406

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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