NM_007294.4:c.4720G>T (p.Asp1574Tyr) is a missense variant in BRCA1 exon 15, located outside all three clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). It is absent from gnomAD v2.1 and v4.1 population databases.¹ The variant meets PM2_Supporting: absent from gnomAD controls in outbred populations, per ENIGMA specifications.² The variant meets BP1_Strong: missense substitution outside clinically important functional domains with no predicted splicing impact (SpliceAI max delta 0.02). Per ENIGMA Figure 1A, missense variants outside domains with SpliceAI ≤0.1 receive BP1_Strong.³ PVS1, PS1, PM5, and several other criteria are not applicable as this is a missense variant without a same-residue pathogenic comparator and without null-variant features.⁴ PS3 could not be assessed through the ENIGMA framework as the variant is not listed in Table 9 (calibrated functional assays). External functional evidence (Carvalho 2007 PMID:17308087, Starita 2018 PMID:29892012) suggests a damaging effect in yeast transcription and multiplex HDR assays, but these have not been calibrated through ENIGMA standards. Human review is recommended. PP4 and BP5 could not be assessed: the variant is absent from the Li et al. 2020 (PMID:31853058) BRCA1 clinical-history likelihood-ratio table.⁵ PS4, PP1, BS2, BS4, and BP7 have no supporting evidence available for this variant. BS3 is not met as functional evidence points toward damaging effect rather than benign.⁶