[Verse 1] A raw VCF is just a rumor in the dark, run it through VEP, SnpEff, ANNOVAR — three tools mark the same lone base with different tongues that speak, Sequence Ontology gives the syntax that we seek. Missense, nonsense, frameshift, splice site call, HGVS writes it clean: c dot, p dot, that's the crawl from DNA to protein, one transcript, one truth— MANE Select's the elder that we lean on for proof. [Chorus] Annotate, filter, classify — that's the chain, gnomAD tells you common, ClinVar tells you pain, VEP finds the letter, ACMG finds the weight, five tiers of certainty from benign to fate: pathogenic, likely, uncertain, likely benign, benign — remember that. [Verse 2] Before you cry disease you check who else is well, gnomAD's a hundred forty thousand genomes to tell if your "rare" mutation's hiding in plain sight— dbSNP remembers names, 1000 Genomes gives sight across the continents, allele frequency's the sieve, one percent and rising means that phenotype won't live in patients that you're chasing, so filter first, then think, constraint before conviction, that's the researcher's link. [Chorus] Annotate, filter, classify — that's the chain, gnomAD tells you common, ClinVar tells you pain, VEP finds the letter, ACMG finds the weight, five tiers of certainty from benign to fate: pathogenic, likely, uncertain, likely benign, benign — remember that. [Verse 3] ClinVar's the courtroom where the submitted evidence piles, OMIM's the family tree of genes and inherited trials, ClinGen curates the panels, tells you what gene's real— then ACMG and AMP hand you the classification wheel: PVS1 for null variants, PM2 for rare and quiet, PP3 computational, BS2 the healthy-carrier alibi. Richards wrote the rulebook back in twenty fifteen ink, document your evidence or the reviewers make you sink. [Bridge] CADD scores the damage deep, REVEL refines the missense guess, AlphaMissense folds the protein, reads the fold's distress, SpliceAI hears the intron whisper where the cut should be, pLI and LOEUF measure how a gene stays whole when it goes empty— the closer LOEUF creeps to zero, the less that gene can fail, constraint is just the body counting losses down the trail. [Verse 4] Not every letter lives inside a coding exon's frame— ENCODE's cCREs mark switches with no protein name, GTEx runs the eQTLs, ties a variant to expression's drop, regulatory reading is the harder puzzle-stop. PharmGKB and CPIC tell you how the body clears the pill, CYP2D6 slow or fast decides if dosage cures or kills. And when you find the thing that nobody asked to know, ethics asks you: who consented, and who gets to say so? [Chorus] Annotate, filter, classify — that's the chain, gnomAD tells you common, ClinVar tells you pain, VEP finds the letter, ACMG finds the weight, five tiers of certainty from benign to fate: pathogenic, likely, uncertain, likely benign, benign — remember that.
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