rs492859

Variant names:

• chr11-105014585-C-A
• rs492859
• NM_004347.5:c.8-5605G>T

Variant summary

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

The NM_001136112.3(CASP5):​c.8-5566G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,076 control chromosomes in the GnomAD database, including 2,023 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 0.15 (2023 hom., cov: 32)
• Consequence: CASP5 NM_001136112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP5	NM_004347.5	MANE Select	c.8-5605G>T		intron	N/A	NP_004338.3
	CASP5	NM_001136112.3		c.8-5566G>T		intron	N/A	NP_001129584.1
	CASP5	NM_001136109.3		c.8-7251G>T		intron	N/A	NP_001129581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP5	ENST00000260315.8	TSL:5 MANE Select	c.8-5605G>T		intron	N/A	ENSP00000260315.3
	CASP5	ENST00000393141.6	TSL:5	c.8-5566G>T		intron	N/A	ENSP00000376849.2
	CASP5	ENST00000526056.5	TSL:5	c.8-5566G>T		intron	N/A	ENSP00000436877.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23126 AN: 151958 Hom.: 2019 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.152 AC: 23152 AN: 152076 Hom.: 2023 Cov.: 32 AF XY: 0.155 AC XY: 11509 AN XY: 74318

African (AFR) AF: 0.0982 AC: 4076 AN: 41504

American (AMR) AF: 0.246 AC: 3763 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5178

South Asian (SAS) AF: 0.110 AC: 532 AN: 4822

European-Finnish (FIN) AF: 0.217 AC: 2293 AN: 10548

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11257 AN: 67962

Other (OTH) AF: 0.161 AC: 339 AN: 2108

Alfa AF: 0.157 Hom.: 985

Bravo AF: 0.154

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.65
PhyloP100		0.96
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: rs492859; hg19: chr11-104885312;