NM_000548.5:c.4006-8C>T is an intronic variant at position -8 of exon 34 in TSC2, not predicted to alter splicing (SpliceAI delta = 0.00).¹ This variant is present in gnomAD at appreciable population frequencies: v2.1 AF=0.2436% (538/220866 alleles, 5 homozygotes) and v4.1 AF=0.3818% (6017/1575890 alleles, 15 homozygotes), with the highest subpopulation frequency in the European (non-Finnish) group at 0.3946% (v2.1) and 0.4712% (v4.1). These frequencies far exceed the expected prevalence of tuberous sclerosis complex (estimated incidence ~1:6000 to 1:10000 live births), meeting BS1 (strong benign).² Five homozygotes are observed in gnomAD v2.1 and 15 homozygotes in gnomAD v4.1. TSC is an autosomal dominant disorder with near-complete penetrance and significant morbidity; the presence of homozygotes in a general population database is incompatible with pathogenicity, meeting BS2 (strong benign).³ This variant has been classified as Benign by 14 clinical diagnostic laboratories and as Likely benign by 5 clinical laboratories in ClinVar (Variation ID 49281), meeting BP6 (supporting benign).⁴ SpliceAI predicts no splicing impact (max delta = 0.00), and the variant is an intronic substitution at a non-canonical splice position, meeting BP4 and BP7 (each supporting benign).⁵ No variant-specific functional studies, de novo observations, cosegregation data, or case-control studies were identified for this variant. The ClinVar criterion-lead submission (SCV000066333, Tuberous sclerosis database) cited PMID:17304050, but the full text of that publication does not mention NM_000548.5:c.4006-8C>T. Classification: Likely Benign. Benign evidence includes BS1 (strong), BS2 (strong), BP4 (supporting), BP6 (supporting), and BP7 (supporting). No pathogenic or likely pathogenic criteria are met. Under the ACMG/AMP 2015 combining criteria, ≥2 strong benign criteria → Likely Benign.⁶