rs2282659

Variant names:

• chr11-105026710-A-G
• rs2282659
• NM_001257118.3:c.1116+132T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000303891 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257118.3. 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
	CASP1	NM_001257118.3	MANE Select	c.1116+132T>C		intron	N/A	NP_001244047.1	P29466-1
	CASP1	NM_033292.4		c.1116+132T>C		intron	N/A	NP_150634.1	P29466-1
	CASP1	NM_001223.5		c.1053+132T>C		intron	N/A	NP_001214.1	P29466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	ENST00000533400.6	TSL:1 MANE Select	c.1116+132T>C		intron	N/A	ENSP00000433138.1	P29466-1
	CASP1	ENST00000436863.7	TSL:1	c.1116+132T>C		intron	N/A	ENSP00000410076.3	P29466-1
	CASP1	ENST00000526568.5	TSL:1	c.837+132T>C		intron	N/A	ENSP00000434250.1	P29466-3

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

African (AFR) AF: 0.199 AC: 2598 AN: 13048

American (AMR) AF: 0.175 AC: 3944 AN: 22480

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 2900 AN: 14608

East Asian (EAS) AF: 0.260 AC: 8323 AN: 32046

South Asian (SAS) AF: 0.222 AC: 10856 AN: 48836

European-Finnish (FIN) AF: 0.226 AC: 7946 AN: 35136

Middle Eastern (MID) AF: 0.158 AC: 340 AN: 2158

European-Non Finnish (NFE) AF: 0.278 AC: 81228 AN: 291664

Other (OTH) AF: 0.248 AC: 6818 AN: 27494

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

African (AFR) AF: 0.207 AC: 8584 AN: 41436

American (AMR) AF: 0.197 AC: 2993 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1280 AN: 5148

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4804

European-Finnish (FIN) AF: 0.226 AC: 2384 AN: 10542

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19051 AN: 67920

Other (OTH) AF: 0.219 AC: 462 AN: 2108

Alfa AF: 0.263 Hom.: 21330

Bravo AF: 0.234

Asia WGS AF: 0.266 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		-1.1
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: rs2282659; hg19: chr11-104897437; COSMIC: COSV52829779; COSMIC: COSV52829779;