11-105006990-C-T

Variant names:

• chr11-105006990-C-T
• rs2282658
• NM_004347.5:c.433+93G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004347.5(CASP5):​c.433+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000567 in 881,888 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: 0.0000057 (0 hom.)
• Consequence: CASP5 NM_004347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 9 publications found

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]

ENSG00000303891 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004347.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP5	NM_004347.5	MANE Select	c.433+93G>A		intron	N/A	NP_004338.3	P51878-1
	CASP5	NM_001136112.3		c.472+93G>A		intron	N/A	NP_001129584.1	P51878-5
	CASP5	NM_001136109.3		c.259+93G>A		intron	N/A	NP_001129581.1	P51878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP5	ENST00000260315.8	TSL:5 MANE Select	c.433+93G>A		intron	N/A	ENSP00000260315.3	P51878-1
	CASP5	ENST00000393141.6	TSL:5	c.472+93G>A		intron	N/A	ENSP00000376849.2	P51878-5
	CASP5	ENST00000526056.5	TSL:5	c.472+93G>A		intron	N/A	ENSP00000436877.1	P51878-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000567 AC: 5 AN: 881888 Hom.: 0 AF XY: 0.00000443 AC XY: 2 AN XY: 451392

African (AFR) AF: 0.00 AC: 0 AN: 20266

American (AMR) AF: 0.00 AC: 0 AN: 28864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17340

East Asian (EAS) AF: 0.00 AC: 0 AN: 36844

South Asian (SAS) AF: 0.00 AC: 0 AN: 59978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45758

Middle Eastern (MID) AF: 0.000683 AC: 3 AN: 4392

European-Non Finnish (NFE) AF: 0.00000319 AC: 2 AN: 627758

Other (OTH) AF: 0.00 AC: 0 AN: 40688

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.90
PhyloP100		-0.33

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

Other links and lift over

dbSNP: rs2282658; hg19: chr11-104877717;