Stacked bar chart showing the VAF distribution in plasma- vs. urine-derived ctDNA. All variants were assigned to five different groups: VAF 3 ≤ 5%, 5 ≤ 10%, 10 ≤ 20%, 20 ≤ 50% and 50–100%. Even though we did not have matched germline samples for our cohort, 88% (n = 1079) of plasma-derived and 87% (n = 1841) of urinary-derived variants showed a VAF below 20%, indicating that the variants are rather of somatic than germline origin. In total, 98% of all variants (n = 3266) displayed a VAF below 50%, which additionally supports this thesis, as germline variants would most likely display a VAF of 50% or 100%.