Introduction to ClinicalVariantR

Overview

ClinicalVariantR is an R / Bioconductor software package that classifies germline sequence variants under the ACMG/AMP 2015 framework from pre-annotated VCF files (VEP CSQ, SnpEff ANN, or ANNOVAR-style INFO fields).

The package exposes an interactive Shiny application with three workflows:

Workflow Inputs Purpose
Group A (full clinical) VCF + clinical log + pedigree Automated criteria plus curator toggles
Group B (rapid) VCF only High-throughput automated classification
Group C (gene panel) VCF + gene list Panel-restricted automated classification

Installation

if (!requireNamespace("BiocManager", quietly = TRUE)) {
    install.packages("BiocManager")
}
BiocManager::install("ClinicalVariantR")

Until the package is accepted on Bioconductor, install from GitHub:

# install.packages("remotes")
remotes::install_github("safarafique/ClinicalVariantR")

Launching the Shiny app

Following Bioconductor Shiny guidelines, package functions return a Shiny app object; the user launches it:

if (requireNamespace("ClinicalVariantR", quietly = TRUE)) {
    stopifnot(is.function(ClinicalVariantR::ClinicalVariantR))
}
# To launch interactively:
# shiny::runApp(ClinicalVariantR())

ClinicalVariantRApp() is an alias of ClinicalVariantR().

For a full walkthrough of launching the app, choosing sample VCFs, Group A/B/C UI checks, and command-line tests, see the companion vignette Running and testing ClinicalVariantR (vignettes/ClinicalVariantR-run-and-test.Rmd).

Input requirements

  • VCF (.vcf or .vcf.gz) with VEP CSQ, SnpEff ANN, or ANNOVAR-style annotation for consequence, gene symbol, transcript, population AF, ClinVar, and in silico scores when available.
  • Optional clinical log and pedigree CSV files for Group A.
  • Optional gene symbol list for Group C.

Default reference tables under inst/extdata/reference/ are placeholders; population and prediction evidence primarily use annotation embedded in the VCF unless curated references are installed (see package README).

Scope and limitations

ClinicalVariantR targets germline SNV and small-indel interpretation. It does not classify somatic variants, structural variants, CNVs, or mitochondrial genomes. Several ACMG criteria require external data (functional assays, phasing, matched pathogenic variants) and are registered as manual or not automated.

See the package NEWS file and GitHub README for version-specific criterion coverage and validation notes.

Session info

sessionInfo()
#> R version 4.6.1 (2026-06-24)
#> Platform: x86_64-pc-linux-gnu
#> Running under: Ubuntu 26.04 LTS
#> 
#> Matrix products: default
#> BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3 
#> LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.32.so;  LAPACK version 3.12.0
#> 
#> locale:
#>  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
#>  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
#>  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
#>  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
#>  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
#> [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
#> 
#> time zone: Etc/UTC
#> tzcode source: system (glibc)
#> 
#> attached base packages:
#> [1] stats     graphics  grDevices utils     datasets  methods   base     
#> 
#> other attached packages:
#> [1] BiocStyle_2.41.0
#> 
#> loaded via a namespace (and not attached):
#>  [1] cli_3.6.6               knitr_1.51              rlang_1.3.0            
#>  [4] xfun_0.60               otel_0.2.0              promises_1.5.0         
#>  [7] shiny_1.14.0            xtable_1.8-8            jsonlite_2.0.0         
#> [10] buildtools_1.0.0        htmltools_0.5.9         maketools_1.3.2        
#> [13] httpuv_1.6.17           sys_3.4.3               sass_0.4.10            
#> [16] rmarkdown_2.31          evaluate_1.0.5          jquerylib_0.1.4        
#> [19] fastmap_1.2.0           yaml_2.3.12             lifecycle_1.0.5        
#> [22] ClinicalVariantR_0.99.0 BiocManager_1.30.27     compiler_4.6.1         
#> [25] Rcpp_1.1.2              later_1.4.8             digest_0.6.39          
#> [28] R6_2.6.1                magrittr_2.0.5          bslib_0.11.0           
#> [31] tools_4.6.1             mime_0.13               cachem_1.1.0