chr11-105024470-G-C

Variant names:

• chr11-105024470-G-C
• rs554344
• ENST00000904258.1:c.*1788C>G

Variant summary

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

The ENST00000904258.1(CASP1):​c.*1788C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,928 control chromosomes in the GnomAD database, including 2,028 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 0.15 (2028 hom., cov: 31)
• Consequence: CASP1 ENST00000904258.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000904258.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP1	ENST00000904258.1		c.*1788C>G		3_prime_UTR	Exon 8 of 8	ENSP00000574317.1
	ENSG00000303891	ENST00000797905.1		n.620-6877G>C		intron	N/A
	ENSG00000303891	ENST00000797910.1		n.144-6877G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23143 AN: 151810 Hom.: 2024 Cov.: 31

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.152 AC: 23169 AN: 151928 Hom.: 2028 Cov.: 31 AF XY: 0.155 AC XY: 11507 AN XY: 74252

African (AFR) AF: 0.0982 AC: 4071 AN: 41466

American (AMR) AF: 0.246 AC: 3750 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3464

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5170

South Asian (SAS) AF: 0.111 AC: 535 AN: 4820

European-Finnish (FIN) AF: 0.217 AC: 2283 AN: 10536

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11304 AN: 67924

Other (OTH) AF: 0.160 AC: 337 AN: 2104

Alfa AF: 0.0818 Hom.: 98

Bravo AF: 0.155

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.32
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs554344; hg19: chr11-104895197;