rs11226580

Variant names:

• chr11-105009912-T-C
• rs11226580
• NM_004347.5:c.8-932A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001136112.3(CASP5):​c.8-893A>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_001136112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

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.8-932A>G		intron	N/A	NP_004338.3
	CASP5	NM_001136112.3		c.8-893A>G		intron	N/A	NP_001129584.1
	CASP5	NM_001136109.3		c.8-2578A>G		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.8-932A>G		intron	N/A	ENSP00000260315.3
	CASP5	ENST00000393141.6	TSL:5	c.8-893A>G		intron	N/A	ENSP00000376849.2
	CASP5	ENST00000526056.5	TSL:5	c.8-893A>G		intron	N/A	ENSP00000436877.1

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0727 AC: 2053 AN: 28244

American (AMR) AF: 0.00800 AC: 102 AN: 12754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3254

East Asian (EAS) AF: 0.00 AC: 0 AN: 4768

South Asian (SAS) AF: 0.00122 AC: 5 AN: 4114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7710

Middle Eastern (MID) AF: 0.00763 AC: 2 AN: 262

European-Non Finnish (NFE) AF: 0.000263 AC: 16 AN: 60770

Other (OTH) AF: 0.0204 AC: 35 AN: 1712

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0437 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism

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: rs11226580; hg19: chr11-104880639;