11-105006990-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136112.3(CASP5):​c.472+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_001136112.3 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136112.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

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

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

African (AFR) AF: 0.572 AC: 11566 AN: 20224

American (AMR) AF: 0.218 AC: 6278 AN: 28830

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 4439 AN: 17326

East Asian (EAS) AF: 0.237 AC: 8744 AN: 36824

South Asian (SAS) AF: 0.257 AC: 15409 AN: 59906

European-Finnish (FIN) AF: 0.304 AC: 13882 AN: 45702

Middle Eastern (MID) AF: 0.184 AC: 806 AN: 4386

European-Non Finnish (NFE) AF: 0.322 AC: 201474 AN: 625274

Other (OTH) AF: 0.315 AC: 12803 AN: 40610

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

African (AFR) AF: 0.585 AC: 24260 AN: 41440

American (AMR) AF: 0.271 AC: 4140 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1110 AN: 5180

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3196 AN: 10562

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23454 AN: 67966

Other (OTH) AF: 0.344 AC: 728 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.26
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52828987;