The combination of variation data with information about regulatory function13 can potentially improve the power to detect pathological non-coding variants. We find that individuals typically harbour several thousands of variants (and several hundred rare variants) in conserved (GERP conservation score >2) UTRs, non-coding RNAs and transcription-factor binding motifs (Table 2). Within experimentally-defined transcription factor binding sites, individuals carry 700-900 conserved motif losses (for the transcription factors analysed, see Supplementary Information), of which 18-69 are rare (<0.5%) and which show strong evidence for being selected against. Motif gains are rarer (~200 per individual at conserved sites) but they also show evidence for an excess of rare variants compared to conserved sites with no functional annotation (Table 2). Many of these changes are likely to have weak, slightly deleterious effects on gene regulation and function.
