chr11-105006990-C-G

Position:

• chr11-105006990-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004347.5(CASP5):​c.433+93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,031,102 control chromosomes in the GnomAD database, including 57,693 homozygotes. 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: 𝑓 0.39 (12762 hom., cov: 32)
  • Exomes 𝑓: 0.31 (44931 hom.)
• Consequence: CASP5 NM_004347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP5	NM_004347.5	c.433+93G>C		intron_variant		ENST00000260315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP5	ENST00000260315.8	c.433+93G>C		intron_variant		5	NM_004347.5	A2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59272 AN: 151902 Hom.: 12736 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.313 AC: 275401 AN: 879082 Hom.: 44931 AF XY: 0.312 AC XY: 140583 AN XY: 450036

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.390 AC: 59353 AN: 152020 Hom.: 12762 Cov.: 32 AF XY: 0.384 AC XY: 28529 AN XY: 74316

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.344

Alfa AF: 0.219 Hom.: 459

Bravo AF: 0.394

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs2282658; hg19: chr11-104877717; COSMIC: COSV52828987;