rs2282659

Positions:

• chr11-105026710-A-G

Variant summary

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

The NM_001257118.3(CASP1):​c.1116+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 639,318 control chromosomes in the GnomAD database, including 21,171 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 0.24 (4600 hom., cov: 32)
  • Exomes 𝑓: 0.26 (16571 hom.)
• Consequence: CASP1 NM_001257118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

CASP1 (HGNC:1499): (caspase 1) This gene encodes a protein which is 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

CASP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.1116+132T>C		intron_variant		ENST00000533400.6	NP_001244047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.1116+132T>C		intron_variant		1	NM_001257118.3	ENSP00000433138.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36643 AN: 151732 Hom.: 4596 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.256 AC: 124953 AN: 487470 Hom.: 16571 Cov.: 5 AF XY: 0.256 AC XY: 66891 AN XY: 260914

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.241 AC: 36665 AN: 151848 Hom.: 4600 Cov.: 32 AF XY: 0.240 AC XY: 17815 AN XY: 74228

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.219

Alfa AF: 0.266 Hom.: 9041

Bravo AF: 0.234

Asia WGS AF: 0.266 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.57

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: rs2282659; hg19: chr11-104897437; COSMIC: COSV52829779; COSMIC: COSV52829779;