Variant chr9-122377927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_001271367.2(PTGS1):c.-204-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,613,848 control chromosomes in the GnomAD database, including 3,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 1356 hom., cov: 33)

Exomes 𝑓: 0.032 ( 1843 hom. )

Consequence

PTGS1
NM_001271367.2 splice_acceptor, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.48

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 -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06387665 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.8, offset of 6, new splice context is: actatccatgccaacaccAGggc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 9-122377927-G-A is Benign according to our data. Variant chr9-122377927-G-A is described in ClinVar as [Benign]. Clinvar id is 1241842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 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.123G>A	p.Gln41Gln	synonymous_variant	3/11	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.123G>A	p.Gln41Gln	synonymous_variant	3/11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.0917

AC:

13950

AN:

152126

Hom.:

1357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.0622

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0766

GnomAD3 exomes

AF:

0.0462

AC:

11613

AN:

251310

Hom.:

678

AF XY:

0.0427

AC XY:

5807

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.0264

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0637

Gnomad SAS exome

AF:

0.0395

Gnomad FIN exome

AF:

0.0308

Gnomad NFE exome

AF:

0.0254

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0320

AC:

46799

AN:

1461604

Hom.:

1843

Cov.:

AF XY:

0.0319

AC XY:

23211

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.0659

Gnomad4 SAS exome

AF:

0.0407

Gnomad4 FIN exome

AF:

0.0278

Gnomad4 NFE exome

AF:

0.0226

Gnomad4 OTH exome

AF:

0.0437

GnomAD4 genome

AF:

0.0918

AC:

13970

AN:

152244

Hom.:

1356

Cov.:

AF XY:

0.0895

AC XY:

6665

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.0617

Gnomad4 SAS

AF:

0.0385

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0758

Alfa

AF:

0.0417

Hom.:

511

Bravo

AF:

0.0998

Asia WGS

AF:

0.0520

AC:

179

AN:

3478

EpiCase

AF:

0.0306

EpiControl

AF:

0.0311

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 08, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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