If you've had whole-genome sequencing (WGS) through a service like Nebula or Dante Labs, or clinical exome sequencing through a hospital, or participated in a research study that returned your variant data — you probably have a VCF file. Maybe two.
VCF stands for Variant Call Format. It's the open-standard file format used by every major sequencing platform to represent genetic variants. Unlike the proprietary file formats of consumer DNA tests (.txt for 23andMe, .csv for AncestryDNA), VCF is a single industry standard, defined by the Global Alliance for Genomics and Health.
What's actually in a VCF
A VCF file lists, for each position in the genome where you differ from the reference, what variant you have. It looks like this (simplified):
##fileformat=VCFv4.2
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SAMPLE
1 27365127 rs1801133 C T . PASS . GT 0/1
1 27370001 rs1801131 T G . PASS . GT 1/1
Each row is a variant:
- CHROM / POS: chromosome and base-pair position
- ID: rsID (the standard variant identifier in dbSNP)
- REF / ALT: reference allele / your alternate allele
- GT: genotype — 0/0 = homozygous reference, 0/1 = heterozygous, 1/1 = homozygous alternate
Why VCF is different from a 23andMe file
Consumer DNA test files (23andMe, AncestryDNA, MyHeritage) record your genotype at every position the chip tested — typically ~600,000 to ~700,000 SNPs. Most of those positions match the reference; only a fraction are variants.
VCF files from sequencing typically record ONLY the positions where you differ from reference. A whole-genome VCF can have 4–5 million variant entries. An exome VCF (just protein-coding regions) has ~30,000–50,000.
Because VCF skips reference matches, analyzing a VCF for "coverage" requires inferring that positions not in the file are reference. Atlagene does this automatically with what we call WGS reference backfill — when a position we want to check isn't in your VCF, we record it as homozygous reference. This brings WGS coverage scores up from a misleading ~10-20% (just the variants you have) to the accurate 80-100% (variants checked).
Where you might have a VCF
- Whole-genome sequencing services: Nebula Genomics, Dante Labs, Veritas (no longer operating in the US), Sano (no longer operating). Files are typically 50–500 MB compressed.
- Clinical exome or panel testing: hospital genetics labs, GeneDx, Invitae, Color, Ambry. Files are smaller (10–50 MB).
- Research studies: All of Us, UK Biobank participants, Manchester Cancer Research Centre cohorts, etc. Often returned in batches with a clinician contact.
- Cancer genomics: tumor-sequencing reports from Foundation Medicine, Caris, Tempus.
How to use a VCF with Atlagene
Atlagene accepts VCF files directly — no conversion required. Auto-detected on upload. WGS files (50+ MB) get a deeper analysis with 7x more variants checked than consumer-array files. Premium tier required for WGS uploads.
For the deepest analysis, your VCF should:
- Cover at least the 21 categories' worth of clinically relevant variants (~700-1500 specific positions)
- Be aligned to GRCh37 or GRCh38 (Atlagene auto-detects)
- Be uncompressed (.vcf) or gzipped (.vcf.gz)
If your VCF is from a specific gene panel (say, just BRCA1/2), Atlagene can still analyze it but coverage outside those genes will be near-zero. WGS or exome VCFs give the most complete picture.
Reading a VCF yourself
If you want to inspect a VCF without any platform:
- Open in any text editor (VCFs are tab-separated text files, despite the size)
- Use
bcftools(open-source command-line tool) for filtering and querying - Use IGV (Integrative Genomics Viewer) for visualization
Search for specific rsIDs by greppling: grep "rs1801133" yourfile.vcf shows your MTHFR C677T status, for example.
Don't try to interpret raw VCF as health information without context. The same variant can be benign or pathogenic depending on cellular context, family history, and other variants — that's what variant interpretation platforms exist to handle.
Privacy notes for VCFs
VCF files are far more identifying than consumer-DNA-test files. They contain your full variant set, which is unique to you and a couple of close relatives. Treat them like medical records:
- Don't email VCFs unencrypted
- Don't upload to platforms without verifying their privacy posture
- Atlagene stores VCFs in AES-256 encrypted, isolated infrastructure (see privacy policy)
Bottom line
VCF is the universal language of clinical and research genomics. If you have one, you have a more complete genetic record than most consumer DNA tests provide. Most genomic-health platforms — including Atlagene — accept VCF directly.
Upload your VCF file to Atlagene — Premium tier required for WGS-size files.