Fig 4. Schematic of Variant Reduction Using a Combined Filter.

The Combined Filter sequentially applies all the filters described in this study. Vertical colored bars reflect relative changes in the content of the variant pool after each filter step. Horizontal colored bars reflect rejected variants upon each filter step. The Strand and Proximity Pre-Filters are applied universally. Then the Affected Kindred/Cross-Cohort Filter (with Shared Segment Filter) is applied. The rejected variant pool in this step primarily eliminates neutral variants. Nonetheless, this rejected pool of variants is assessed for co-occurrence with rare dbSNP variants with known pathological function. Rejected variants that positively co-occur in the Rare Clinical Variants dataset are re-introduced (thin red arrow). Database-dependent filters are sequentially applied. Red bars reflect potential XLID variants that may be of functional interest. Green bars reflect variants that are likely sequencing errors. Blue bars reflect variants that are likely neutral in XLID etiology.