Variant 11-105007200-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004347.5(CASP5):c.316A>G(p.Thr106Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,612,524 control chromosomes in the GnomAD database, including 162,981 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.49 ( 18606 hom., cov: 32)

Exomes 𝑓: 0.44 ( 144375 hom. )

Consequence

CASP5
NM_004347.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.150

Variant links:

Genes affected

CASP5 (HGNC:1506): (caspase 5) 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. Overexpression of the active form of this enzyme induces apoptosis in fibroblasts. Max, a central component of the Myc/Max/Mad transcription regulation network important for cell growth, differentiation, and apoptosis, is cleaved by this protein; this process requires Fas-mediated dephosphorylation of Max. The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

CASP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0572106E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP5	NM_004347.5 link	c.316A>G	p.Thr106Ala	missense_variant	Exon 3 of 10	ENST00000260315.8	NP_004338.3	P51878-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP5	ENST00000260315.8 link	c.316A>G	p.Thr106Ala	missense_variant	Exon 3 of 10	5	NM_004347.5	ENSP00000260315.3		P51878-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73689

AN:

151856

Hom.:

18579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.434

AC:

108969

AN:

251040

Hom.:

24781

AF XY:

0.427

AC XY:

57861

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.217

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.449

Gnomad NFE exome

AF:

0.445

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.441

AC:

643673

AN:

1460550

Hom.:

144375

Cov.:

AF XY:

0.437

AC XY:

317390

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.615

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.447

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.486

AC:

73784

AN:

151974

Hom.:

18606

Cov.:

AF XY:

0.484

AC XY:

35925

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.442

Hom.:

37758

Bravo

AF:

0.492

TwinsUK

AF:

0.457

AC:

1695

ALSPAC

AF:

0.446

AC:

1719

ESP6500AA

AF:

0.614

AC:

2704

ESP6500EA

AF:

0.441

AC:

3788

ExAC

AF:

0.435

AC:

52777

Asia WGS

AF:

0.351

AC:

1218

AN:

3478

EpiCase

AF:

0.428

EpiControl

AF:

0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.90

DANN

Benign

0.12

DEOGEN2

Benign

0.016

.;T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.20

T;T;T;.;T

MetaRNN

Benign

0.000011

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.9

.;N;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

1.3

N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.017

MPC

0.19

ClinPred

0.0036

GERP RS

2.5

Varity_R

0.025

gMVP

0.049

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over