rs518604

Variant names:

• chr11-104998504-G-A
• rs518604
• NM_004347.5:c.1096+381C>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.1096+381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,830 control chromosomes in the GnomAD database, including 25,848 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 0.58 (25848 hom., cov: 31)
• Consequence: CASP5 NM_004347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 8 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP5	NM_004347.5	c.1096+381C>T		intron_variant	Intron 7 of 9	ENST00000260315.8	NP_004338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP5	ENST00000260315.8	c.1096+381C>T		intron_variant	Intron 7 of 9	5	NM_004347.5	ENSP00000260315.3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87950 AN: 151712 Hom.: 25834 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.580 AC: 88000 AN: 151830 Hom.: 25848 Cov.: 31 AF XY: 0.581 AC XY: 43132 AN XY: 74210

African (AFR) AF: 0.604 AC: 24972 AN: 41348

American (AMR) AF: 0.496 AC: 7558 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2320 AN: 3464

East Asian (EAS) AF: 0.768 AC: 3964 AN: 5164

South Asian (SAS) AF: 0.614 AC: 2952 AN: 4808

European-Finnish (FIN) AF: 0.582 AC: 6136 AN: 10542

Middle Eastern (MID) AF: 0.790 AC: 229 AN: 290

European-Non Finnish (NFE) AF: 0.560 AC: 38039 AN: 67942

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.573 Hom.: 33005

Bravo AF: 0.575

Asia WGS AF: 0.688 AC: 2391 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.28
PhyloP100		-0.024
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: rs518604; hg19: chr11-104869231;