rs568910

Positions:

• chr11-105033843-A-C

Variant summary

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

The NM_001257118.3(CASP1):​c.274+365T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 573,094 control chromosomes in the GnomAD database, including 9,467 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 0.18 (2539 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6928 hom.)
• Consequence: CASP1 NM_001257118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.274+365T>G		intron_variant		ENST00000533400.6	NP_001244047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.274+365T>G		intron_variant		1	NM_001257118.3	ENSP00000433138.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26719 AN: 152086 Hom.: 2537 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.167 AC: 70122 AN: 420890 Hom.: 6928 AF XY: 0.159 AC XY: 37691 AN XY: 237256

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.00207

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.176 AC: 26740 AN: 152204 Hom.: 2539 Cov.: 32 AF XY: 0.177 AC XY: 13150 AN XY: 74402

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.182

Alfa AF: 0.163 Hom.: 978

Bravo AF: 0.181

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs568910; hg19: chr11-104904570;