rs11226580

Positions:

• chr11-105009912-T-C

Variant summary

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

The NM_004347.5(CASP5):​c.8-932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 124,430 control chromosomes in the GnomAD database, including 86 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 0.018 (86 hom., cov: 24)
• Consequence: CASP5 NM_004347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP5	NM_004347.5	c.8-932A>G		intron_variant		ENST00000260315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP5	ENST00000260315.8	c.8-932A>G		intron_variant		5	NM_004347.5	A2

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2208 AN: 124418 Hom.: 85 Cov.: 24

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00801

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00121

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00709

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.0205

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

GnomAD4 genome AF: 0.0178 AC: 2213 AN: 124430 Hom.: 86 Cov.: 24 AF XY: 0.0163 AC XY: 980 AN XY: 60246

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.00800

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000263

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0437 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
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: rs11226580; hg19: chr11-104880639;