11-105033843-A-G

Variant names:

• chr11-105033843-A-G
• rs568910
• NM_001257118.3:c.274+365T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001257118.3(CASP1):​c.274+365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASP1 NM_001257118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.274+365T>C		intron_variant	Intron 2 of 8	ENST00000533400.6	NP_001244047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.274+365T>C		intron_variant	Intron 2 of 8	1	NM_001257118.3	ENSP00000433138.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000237 AC: 1 AN: 421228 Hom.: 0 AF XY: 0.00000421 AC XY: 1 AN XY: 237416

African (AFR) AF: 0.00 AC: 0 AN: 12264

American (AMR) AF: 0.00 AC: 0 AN: 34308

Ashkenazi Jewish (ASJ) AF: 0.0000724 AC: 1 AN: 13820

East Asian (EAS) AF: 0.00 AC: 0 AN: 18332

South Asian (SAS) AF: 0.00 AC: 0 AN: 64828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 233500

Other (OTH) AF: 0.00 AC: 0 AN: 20738

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.50

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: rs568910; hg19: chr11-104904570;