rs530537

Variant names:

• chr11-105027786-T-C
• rs530537
• NM_001257118.3:c.1007-835A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033292.4(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_033292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 19 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033292.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	NM_001257118.3	MANE Select	c.1007-835A>G		intron	N/A	NP_001244047.1
	CASP1	NM_033292.4		c.1007-835A>G		intron	N/A	NP_150634.1
	CASP1	NM_001223.5		c.944-835A>G		intron	N/A	NP_001214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	ENST00000533400.6	TSL:1 MANE Select	c.1007-835A>G		intron	N/A	ENSP00000433138.1
	CASP1	ENST00000436863.7	TSL:1	c.1007-835A>G		intron	N/A	ENSP00000410076.3
	CASP1	ENST00000526568.5	TSL:1	c.728-835A>G		intron	N/A	ENSP00000434250.1

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

African (AFR) AF: 0.612 AC: 25368 AN: 41456

American (AMR) AF: 0.486 AC: 7396 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1309 AN: 5164

South Asian (SAS) AF: 0.362 AC: 1745 AN: 4826

European-Finnish (FIN) AF: 0.444 AC: 4690 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30478 AN: 67916

Other (OTH) AF: 0.458 AC: 962 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.8
DANN	Benign	0.55
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs530537; hg19: chr11-104898513;