11-104967744-C-T

Variant names:

• chr11-104967744-C-T
• rs1944900
• NM_001225.4:c.7+775G>A

Variant summary

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

The NM_001225.4(CASP4):​c.7+775G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,914 control chromosomes in the GnomAD database, including 6,593 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 0.26 (6593 hom., cov: 32)
• Consequence: CASP4 NM_001225.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 6 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]

LOC124902813 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP4	NM_001225.4	c.7+775G>A		intron_variant	Intron 1 of 8	ENST00000444739.7	NP_001216.1
LOC124902813	XR_007062986.1	n.7302C>T		non_coding_transcript_exon_variant	Exon 1 of 2
CASP4	NM_033306.3	c.-261+775G>A		intron_variant	Intron 1 of 9		NP_150649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP4	ENST00000444739.7	c.7+775G>A		intron_variant	Intron 1 of 8	1	NM_001225.4	ENSP00000388566.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39874 AN: 151796 Hom.: 6567 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.263 AC: 39946 AN: 151914 Hom.: 6593 Cov.: 32 AF XY: 0.262 AC XY: 19467 AN XY: 74234

African (AFR) AF: 0.464 AC: 19196 AN: 41406

American (AMR) AF: 0.204 AC: 3110 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3462

East Asian (EAS) AF: 0.0250 AC: 129 AN: 5158

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4812

European-Finnish (FIN) AF: 0.215 AC: 2264 AN: 10542

Middle Eastern (MID) AF: 0.248 AC: 72 AN: 290

European-Non Finnish (NFE) AF: 0.184 AC: 12501 AN: 67962

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.218 Hom.: 8158

Bravo AF: 0.273

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		-0.20
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: rs1944900; hg19: chr11-104838471;