Variant Browser

The Variant Browser is the central tool for exploring and analyzing genomic variants in VariantMiner. It provides a powerful, interactive interface for browsing millions of variants with advanced filtering, sorting, and annotation capabilities.

Overview

The Variant Browser enables you to:

• Browse variants from processed VCF files

• Apply filters to narrow down variant sets

• View annotations from multiple databases

• Classify variants using ACMG guidelines

• Add comments for collaborative analysis

• Export results for external analysis

• Create reports from selected variants

Accessing the Variant Browser

From Different Contexts

From Files:

1. Navigate to Files in the main menu

2. Find your processed VCF file

3. Click "Browse Variants" next to the file

From Orders:

1. Go to Orders and select an order

2. Click the "Variants" tab

3. Variant browser loads with order-specific data

From Samples:

1. Navigate to Samples and select a sample

2. Click "View Variants" in the sample details

3. Browser shows variants specific to that sample

Direct Access:

1. Click "Variants" in the main navigation

2. Select files or orders to browse

3. Choose variant view configuration

Browser Interface

Main Components

The Variant Browser showing filtered results with annotation columns

Header Section:

• File/Order Information: Shows current data source

• Variant Count: Total variants and filtered count

• View Selector: Choose or create custom views

• Filter Panel Toggle: Show/hide advanced filters

• Export Options: Download results in various formats

Filter Panel:

• Quick Filters: Common filtering options

• Advanced Filters: Detailed filtering criteria

• Saved Filters: Previously saved filter combinations

• Filter Summary: Currently applied filters

Variant Table:

• Sortable Columns: Click headers to sort

• Customizable Columns: Add/remove columns

• Row Selection: Select variants for actions

• Pagination: Navigate through large result sets

Detail Panel:

• Variant Details: Comprehensive variant information

• Annotations: External database annotations

• Classification: ACMG pathogenicity assessment

• Comments: User and team comments

Column Configuration

Default Columns

The browser starts with essential columns:

• Chromosome: Genomic chromosome

• Position: Genomic coordinate

• Reference: Reference allele

• Alternate: Alternate allele

• Gene: Associated gene symbol

• Consequence: Variant effect (e.g., missense, synonymous)

• Quality: Variant quality score

• Depth: Read depth at position

Adding Columns

To customize your view:

1. Click "Customize Columns" button

2. Select from available annotation fields:

   • Population frequencies (gnomAD, 1000 Genomes)

   • Pathogenicity predictions (SIFT, PolyPhen, CADD)

   • Clinical annotations (ClinVar, HGMD)

   • Functional annotations (Consequence details, protein changes)

   • Quality metrics (Genotype quality, allele balance)

3. Arrange column order by dragging

4. Set column widths for optimal viewing

5. Save as view for future use

Column Types and Functions

Genomic Coordinates:

• Clickable links to genome browsers

• Automatic coordinate validation

• Support for different genome builds

Gene Information:

• Links to gene databases (OMIM, GeneCards)

• Gene synonym recognition

• Transcript-specific annotations

Quality Metrics:

• Color-coded quality indicators

• Sortable numeric values

• Filter-friendly formatting

Frequency Data:

• Population-specific frequencies

• Conditional formatting for rare variants

• Multiple population databases

Filtering System

Quick Filters

Commonly used filters are readily available:

Quality Filters:

• High Quality Only: QUAL > 30, DP > 10

• Pass Filters: Only variants passing quality filters

• High Confidence: Stringent quality criteria

Frequency Filters:

• Rare Variants: MAF < 1% in all populations

• Very Rare: MAF < 0.1%

• Novel Variants: Not in population databases

Impact Filters:

• High Impact: Stop-gain, frameshift, splice-site

• Moderate Impact: Missense, in-frame indels

• Coding Variants: All protein-coding changes

Advanced Filtering

Genomic Region:

Chromosome: 1, 2, 3, ..., X, Y
Position Range: 12345678-12456789
Gene List: BRCA1, BRCA2, TP53
Region BED File: Upload BED file with regions

Variant Type:

• SNVs: Single nucleotide variants

• Indels: Insertions and deletions

• CNVs: Copy number variants

• SVs: Structural variants

Functional Impact:

• Consequence Types: Specific variant consequences

• Protein Changes: Amino acid substitutions

• Splice Effects: Splice site predictions

• Regulatory Regions: Non-coding regulatory variants

Population Frequency:

• Database Selection: Choose population databases

• Population Groups: Specific ethnic populations

• Frequency Thresholds: Custom frequency cutoffs

• Missing Data Handling: Include/exclude variants without frequency data

Clinical Significance:

• ClinVar Classifications: Pathogenic, likely pathogenic, etc.

• Disease Associations: Specific disease contexts

• Review Status: ClinVar review confidence levels

• Conflicting Interpretations: Handle classification conflicts

Filter Combinations

Create complex filters using Boolean logic:

• AND conditions: All criteria must be met

• OR conditions: Any criteria can be met

• NOT conditions: Exclude specific criteria

• Nested conditions: Complex logical combinations

Example Complex Filter:

(Gene IN [BRCA1, BRCA2, TP53] AND Consequence = missense_variant)
OR
(MAF < 0.01 AND ClinVar_Significance = Pathogenic)
AND NOT
(Quality < 30 OR Depth < 10)

Variant Details

Comprehensive Information

Click any variant to view detailed information:

Detailed variant information including annotations and clinical significance

Basic Variant Information:

• Genomic coordinates and alleles

• Variant type and size

• Zygosity information

• Allele frequencies in sample

Gene and Transcript Details:

• Affected genes and transcripts

• Consequence predictions

• Protein changes (HGVS notation)

• Splice site predictions

Population Frequencies:

• gnomAD population frequencies

• 1000 Genomes Project data

• Population-specific frequencies

• Allele count information

Pathogenicity Predictions:

• SIFT deleteriousness scores

• PolyPhen-2 predictions

• CADD pathogenicity scores

• Combined predictor scores

Clinical Annotations:

• ClinVar classifications

• Disease associations

• Literature references

• Review status and conflicts

Quality Information:

• Variant quality scores

• Read depth and coverage

• Genotype quality

• Filter status

External Links

Direct links to external resources:

• UCSC Genome Browser: Genomic context

• Ensembl: Gene and transcript information

• ClinVar: Clinical significance

• dbSNP: Variant database

• PubMed: Relevant literature

Variant Classification

ACMG Guidelines

VariantMiner supports ACMG/AMP variant classification:

Classification Categories:

• Pathogenic (P): Clearly disease-causing

• Likely Pathogenic (LP): Probably disease-causing

• Uncertain Significance (VUS): Unknown significance

• Likely Benign (LB): Probably not disease-causing

• Benign (B): Clearly not disease-causing

Classification Interface

To classify a variant:

1. Select variant in the browser

2. Click "Classify" button

3. Choose evidence criteria based on ACMG guidelines

4. Add supporting evidence and references

5. Set classification level based on evidence

6. Save classification with optional comments

Evidence Criteria

ACMG evidence types available:

• Pathogenic Evidence: PVS1, PS1-4, PM1-6, PP1-5

• Benign Evidence: BA1, BS1-4, BP1-7

• Strength Levels: Very strong, strong, moderate, supporting

Collaborative Classification

• Team Reviews: Multiple users can review classifications

• Comment Threads: Discussion on classification decisions

• Version History: Track classification changes over time

• Approval Workflow: Institutional approval processes

Sorting and Navigation

Sorting Options

Click column headers to sort:

• Single Column: Sort by one criterion

• Multi-Column: Sort by multiple criteria with priority

• Custom Sort: Define complex sorting rules

• Saved Sorts: Save frequently used sorting configurations

Navigation Tools

• Pagination: Navigate through large result sets

• Jump to Position: Go directly to genomic coordinates

• Bookmark Variants: Save interesting variants for later

• Search Within Results: Find specific variants in filtered results

Performance Optimization

• Lazy Loading: Load data as you scroll

• Result Caching: Cache filtered results for faster access

• Progressive Enhancement: Show summary first, details on demand

• Background Processing: Continue analysis while browsing

Export and Sharing

Export Formats

Export filtered variants in multiple formats:

• CSV: Spreadsheet-compatible format

• TSV: Tab-separated values

• VCF: Standard variant call format

• JSON: Machine-readable format

• PDF: Formatted report

Sharing Options

• Share Links: Send filtered view URLs to colleagues

• Embedded Views: Embed browser in external applications

• API Access: Programmatic access to filtered results

• Report Integration: Include variants in clinical reports

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Ready to create custom views? Continue to Custom Views & Filters to learn about saving and sharing your browser configurations.