rs3181318

Positions:

• chr11-105009313-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004347.5(CASP5):​c.8-333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,470 control chromosomes in the GnomAD database, including 12,661 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 0.39 (12661 hom., cov: 30)
• Consequence: CASP5 NM_004347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

Genes affected

CASP5 (HGNC:1506): (caspase 5) This gene encodes 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 two subunits, large and small, that dimerize to form the active enzyme. Overexpression of the active form of this enzyme induces apoptosis in fibroblasts. Max, a central component of the Myc/Max/Mad transcription regulation network important for cell growth, differentiation, and apoptosis, is cleaved by this protein; this process requires Fas-mediated dephosphorylation of Max. The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP5	NM_004347.5	c.8-333C>T		intron_variant		ENST00000260315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP5	ENST00000260315.8	c.8-333C>T		intron_variant		5	NM_004347.5	A2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58924 AN: 151356 Hom.: 12636 Cov.: 30

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.390 AC: 59002 AN: 151470 Hom.: 12661 Cov.: 30 AF XY: 0.383 AC XY: 28368 AN XY: 74026

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.343

Alfa AF: 0.366 Hom.: 2168

Bravo AF: 0.393

Asia WGS AF: 0.285 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.7
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs3181318; hg19: chr11-104880040;