rs3181318

Variant names:

• chr11-105009313-G-A
• rs3181318
• NM_004347.5:c.8-333C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000303891 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CASP5	NM_004347.5	c.8-333C>T		intron_variant	Intron 1 of 9	ENST00000260315.8	NP_004338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP5	ENST00000260315.8	c.8-333C>T		intron_variant	Intron 1 of 9	5	NM_004347.5	ENSP00000260315.3

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

African (AFR) AF: 0.585 AC: 24176 AN: 41342

American (AMR) AF: 0.270 AC: 4101 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1101 AN: 5142

South Asian (SAS) AF: 0.256 AC: 1231 AN: 4804

European-Finnish (FIN) AF: 0.303 AC: 3187 AN: 10528

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23272 AN: 67690

Other (OTH) AF: 0.343 AC: 721 AN: 2100

Alfa AF: 0.372 Hom.: 2295

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
PhyloP100		0.67
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: rs3181318; hg19: chr11-104880040;