11-104948606-C-T

Variant names:

• chr11-104948606-C-T
• rs55901059
• NM_001225.4:c.852G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001225.4(CASP4):​c.852G>A​(p.Glu284Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CASP4 NM_001225.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 0 publications found

Genes affected

CASP4 (HGNC:1505): (caspase 4) This gene encodes a protein that 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 composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000303891 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001225.4. 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
	CASP4	NM_001225.4	MANE Select	c.852G>A	p.Glu284Glu	synonymous	Exon 6 of 9	NP_001216.1	P49662-1
	CASP4	NM_033306.3		c.684G>A	p.Glu228Glu	synonymous	Exon 7 of 10	NP_150649.1	P49662-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP4	ENST00000444739.7	TSL:1 MANE Select	c.852G>A	p.Glu284Glu	synonymous	Exon 6 of 9	ENSP00000388566.2	P49662-1
	CASP4	ENST00000393150.7	TSL:1	c.684G>A	p.Glu228Glu	synonymous	Exon 6 of 9	ENSP00000376857.3	P49662-2
	CASP4	ENST00000533730.5	TSL:1	n.932G>A		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459210 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725832

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110464

Other (OTH) AF: 0.0000166 AC: 1 AN: 60262

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.31
PhyloP100		-2.0

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: rs55901059; hg19: chr11-104819333;