This is a duplicate of:
- Do People Import Vcf Files Into Databases? from 5.4 years ago and
- Which Type Of Database Systems Are More Appropriate For Storing Information Extracted From Vcf Files from 3.5 years ago.
Nevertheless, I found the answers on the second post enlightening, and 3.5 years later it seems worthwhile to have an update from the community (and @lh3) on how you deal with these issues.
Notably, @Aaronquinlan's gemini from the second most upvoted answer to question #2 is still under active development. Are people using it? What else are people doing?
If I need to query the contents in the VCF, especially large ones like ExAC, I normally use HDF5.