11-105027786-T-C

Position:

• chr11-105027786-T-C

Variant summary

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

The NM_001257118.3(CASP1):​c.1007-835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,920 control chromosomes in the GnomAD database, including 18,472 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 0.49 (18472 hom., cov: 32)
• Consequence: CASP1 NM_001257118.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.1007-835A>G		intron_variant		ENST00000533400.6	NP_001244047.1
LOC124902742	XR_007062869.1	n.41-3561T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.1007-835A>G		intron_variant		1	NM_001257118.3	ENSP00000433138	P2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73596 AN: 151802 Hom.: 18445 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 73690 AN: 151920 Hom.: 18472 Cov.: 32 AF XY: 0.484 AC XY: 35897 AN XY: 74230

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.458

Alfa AF: 0.474 Hom.: 2185

Bravo AF: 0.492

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.8
DANN	Benign	0.55

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: rs530537; hg19: chr11-104898513;