chr11-105033843-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	NM_001257118.3	MANE Select	c.274+365T>G		intron	N/A	NP_001244047.1
	CASP1	NM_033292.4		c.274+365T>G		intron	N/A	NP_150634.1
	CASP1	NM_001223.5		c.274+365T>G		intron	N/A	NP_001214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	ENST00000533400.6	TSL:1 MANE Select	c.274+365T>G		intron	N/A	ENSP00000433138.1
	CASP1	ENST00000436863.7	TSL:1	c.274+365T>G		intron	N/A	ENSP00000410076.3
	CASP1	ENST00000526568.5	TSL:1	c.58+581T>G		intron	N/A	ENSP00000434250.1

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

African (AFR) AF: 0.178 AC: 2176 AN: 12242

American (AMR) AF: 0.329 AC: 11261 AN: 34262

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 2290 AN: 13798

East Asian (EAS) AF: 0.00207 AC: 38 AN: 18332

South Asian (SAS) AF: 0.108 AC: 7025 AN: 64822

European-Finnish (FIN) AF: 0.217 AC: 4411 AN: 20292

Middle Eastern (MID) AF: 0.105 AC: 328 AN: 3132

European-Non Finnish (NFE) AF: 0.168 AC: 39235 AN: 233286

Other (OTH) AF: 0.162 AC: 3358 AN: 20724

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

African (AFR) AF: 0.178 AC: 7401 AN: 41532

American (AMR) AF: 0.254 AC: 3887 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.112 AC: 539 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11335 AN: 68006

Other (OTH) AF: 0.182 AC: 385 AN: 2116

Alfa AF: 0.169 Hom.: 3969

Bravo AF: 0.181

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs568910; hg19: chr11-104904570;