Variant rs762297913 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001372051.1(CASP8):c.286G>A(p.Ala96Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CASP8
NM_001372051.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.25

Variant links:

Genes affected

CASP8 (HGNC:1509): (caspase 8) 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 composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]

CASP8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41760427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP8	NM_001372051.1 linkuse as main transcript	c.286G>A	p.Ala96Thr	missense_variant	2/9	ENST00000673742.1	NP_001358980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP8	ENST00000673742.1 linkuse as main transcript	c.286G>A	p.Ala96Thr	missense_variant	2/9		NM_001372051.1	ENSP00000501268	P1	Q14790-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460414

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;T;.;T;.;.;T;.;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

T;T;D;D;T;T;T;T;T;T;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.42

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.1

M;M;M;.;M;.;.;.;.;M;.

MutationTaster

Benign

0.97

D;D;D;D;D;D;D;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.44

T;T;T;T;D;D;T;D;D;T;D

Sift4G

Benign

0.29

T;T;T;D;D;D;T;D;D;T;D

Polyphen

1.0

D;P;D;.;D;.;D;.;P;P;.

Vest4

0.42

MutPred

0.37

Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);.;Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);Gain of phosphorylation at A96 (P = 0.1039);

MVP

0.95

MPC

0.95

ClinPred

0.87

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over