Variant rs4645983 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001229.5(CASP9):c.93C>T(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,539,048 control chromosomes in the GnomAD database, including 41,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6670 hom., cov: 33)

Exomes 𝑓: 0.22 ( 34768 hom. )

Consequence

CASP9
NM_001229.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.149

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-15524108-G-A is Benign according to our data. Variant chr1-15524108-G-A is described in ClinVar as [Benign]. Clinvar id is 3059411.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.149 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP9	NM_001229.5 link	c.93C>T	p.Ser31Ser	synonymous_variant	1/9	ENST00000333868.10	NP_001220.2	P55211-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10 link	c.93C>T	p.Ser31Ser	synonymous_variant	1/9	1	NM_001229.5	ENSP00000330237.5		P55211-1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41977

AN:

151892

Hom.:

6643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.269

GnomAD3 exomes

AF:

0.204

AC:

28052

AN:

137730

Hom.:

3247

AF XY:

0.204

AC XY:

15329

AN XY:

75068

show subpopulations

Gnomad AFR exome

AF:

0.404

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.0641

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.219

AC:

303378

AN:

1387044

Hom.:

34768

Cov.:

AF XY:

0.219

AC XY:

149764

AN XY:

685208

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.0784

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.277

AC:

42039

AN:

152004

Hom.:

6670

Cov.:

AF XY:

0.274

AC XY:

20337

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.426

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0650

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.233

Hom.:

3529

Bravo

AF:

0.276

Asia WGS

AF:

0.161

AC:

556

AN:

3470

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 08, 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

-0.68

CADD

Benign

8.4

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

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