Variant rs2020902 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001229.5(CASP9):c.453+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,170 control chromosomes in the GnomAD database, including 15,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1256 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14228 hom. )

Consequence

CASP9
NM_001229.5 splice_region, intron

Scores

Splicing: ADA: 0.00004793

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.435

Variant links:

Genes affected

CASP9 (HGNC:1511): (caspase 9) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

CASP9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-15507865-A-G is Benign according to our data. Variant chr1-15507865-A-G is described in ClinVar as [Benign]. Clinvar id is 3060608.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP9	NM_001229.5 linkuse as main transcript	c.453+8T>C		splice_region_variant, intron_variant		ENST00000333868.10	NP_001220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10 linkuse as main transcript	c.453+8T>C		splice_region_variant, intron_variant		1	NM_001229.5	ENSP00000330237	P1	P55211-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18675

AN:

152136

Hom.:

1253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.0389

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.122

AC:

30545

AN:

251294

Hom.:

2091

AF XY:

0.125

AC XY:

16923

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.0869

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0358

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.136

AC:

199170

AN:

1460916

Hom.:

14228

Cov.:

AF XY:

0.136

AC XY:

98941

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.0872

Gnomad4 AMR exome

AF:

0.0881

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.0544

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.123

AC:

18680

AN:

152254

Hom.:

1256

Cov.:

AF XY:

0.121

AC XY:

8983

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0919

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.0390

Gnomad4 SAS

AF:

0.0905

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.139

Hom.:

2525

Bravo

AF:

0.118

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.145

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CASP9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.77

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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