chr11-104958010-T-C

Variant names:

• chr11-104958010-T-C
• rs7123277
• NM_001225.4:c.8-3009A>G

Variant summary

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

The NM_001225.4(CASP4):​c.8-3009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,100 control chromosomes in the GnomAD database, including 2,436 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 0.17 (2436 hom., cov: 33)
• Consequence: CASP4 NM_001225.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

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.8-3009A>G		intron	N/A	NP_001216.1	P49662-1
	CASP4	NM_033306.3		c.-260-1315A>G		intron	N/A	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.8-3009A>G		intron	N/A	ENSP00000388566.2	P49662-1
	CASP4	ENST00000533730.5	TSL:1	n.30-3009A>G		intron	N/A
	CASP4	ENST00000417440.2	TSL:3	c.8-3009A>G		intron	N/A	ENSP00000401673.2	E9PMT1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25437 AN: 151982 Hom.: 2437 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.167 AC: 25446 AN: 152100 Hom.: 2436 Cov.: 33 AF XY: 0.168 AC XY: 12510 AN XY: 74352

African (AFR) AF: 0.253 AC: 10491 AN: 41466

American (AMR) AF: 0.136 AC: 2077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3466

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5186

South Asian (SAS) AF: 0.176 AC: 848 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9091 AN: 67984

Other (OTH) AF: 0.146 AC: 308 AN: 2108

Alfa AF: 0.157 Hom.: 296

Bravo AF: 0.169

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.70
PhyloP100		0.86
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: rs7123277; hg19: chr11-104828737;