rs556205

Positions:

• chr11-105027281-T-G

Variant summary

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

The NM_001257118.3(CASP1):​c.1007-330A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 529,358 control chromosomes in the GnomAD database, including 3,222 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 0.095 (975 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2247 hom.)
• Consequence: CASP1 NM_001257118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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]

LOC124902742 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.1007-330A>C		intron_variant		ENST00000533400.6	NP_001244047.1
LOC124902742	XR_007062869.1	n.41-4066T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.1007-330A>C		intron_variant		1	NM_001257118.3	ENSP00000433138	P2

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14379 AN: 151998 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0996 AC: 37567 AN: 377242 Hom.: 2247 AF XY: 0.0989 AC XY: 19565 AN XY: 197830

Gnomad4 AFR exome AF: 0.0301

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.00126

Gnomad4 SAS exome AF: 0.0925

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0999

GnomAD4 genome AF: 0.0946 AC: 14393 AN: 152116 Hom.: 975 Cov.: 32 AF XY: 0.0993 AC XY: 7386 AN XY: 74366

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0998 Hom.: 155

Bravo AF: 0.0981

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.71

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: rs556205; hg19: chr11-104898008;