rs748239649

Variant names:

• chr11-104995826-T-A
• rs748239649
• NM_004347.5:c.1223A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-104995826-T-A
• chr11-104995826-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004347.5(CASP5):​c.1223A>T​(p.Glu408Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP5 NM_004347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP5	NM_004347.5	c.1223A>T	p.Glu408Val	missense_variant	Exon 9 of 10	ENST00000260315.8	NP_004338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP5	ENST00000260315.8	c.1223A>T	p.Glu408Val	missense_variant	Exon 9 of 10	5	NM_004347.5	ENSP00000260315.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	.;.;T;.;.;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T;T;T;T;.;.
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.4	.;.;M;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.4	D;D;D;D;D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.36
MutPred		0.66		.;.;Loss of disorder (P = 0.0135);.;.;.;
MVP		0.52
MPC		0.84
ClinPred		1.0	D
GERP RS		1.6
Varity_R		0.90
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs748239649; hg19: chr11-104866553;