Extended Data Fig. 3: Outlier filtering.
Visualization of different cases for the rare variant outlier filter (corresponds to Filter 3 in Extended Data Fig. 4). a, Exons 1, 3 and 4 were annotated in SpliceMap. Exon 2 is a novel exon detected on an individual whose splice sites are not in SpliceMap. If there exists a rare variant within 250 bp of any splice site (in SpliceMap or not) that shares a junction with either the donor or acceptor site of the outlier event, the outlier passes the ‘rare variant filter’. Cases 1 and 2: The individual has a rare variant within 250 bp of either the donor site of exon 1 or the acceptor site of exon 2, which are the splice sites of the outlier junction. Importantly, exon 2 was not quantified by SpliceMap, but the outlier filter solely depends on split reads. Case 3: The individual has a rare variant within 250 bp of the donor site of exon 2. However, this donor site is not part of the outlier event. Case 4: The individual has a rare variant within 250 bp of the acceptor site of exon 3, which forms a splicing junction with the donor site of exon 1. Case 5: The individual has two rare variants, one further than 250 bp of any splice site, the other within 250 bp of the acceptor site of exon 4. Notably, a variant can be far from the outlier junction and still be involved in the outlier event. b, Exon elongation detected as a splicing efficiency outlier. For splicing efficiency outliers, only the affected splice-site with altered splicing efficiency is considered for the variant filter. Case 1: The individual has a rare variant within 250 bp of the donor site of exon 1. Case 2: The individual has a rare variant that overlaps the acceptor site of the elongated exon 3, but is further than 250 bp from the acceptor site of exon 3. Case 3: The individual has a rare variant within 250 bp of the acceptor site of exon 3. Case 4: The individual has a rare variant within 250 bp of the donor site of exon 3, but the donor is not related to the exon elongation.
