Variant Frequency Filters

Small Variants

Connected Insights includes the Population filter that filters small variants based on the population allele frequency provided in the gnomAD database or custom annotations (refer to Custom Annotations).

Copy Number and Structural Variants

The same Population filter is used to filter CNVs and SVs. For these variant categories, the filter uses the aggregate population allele frequency as calculated by Connected Insights based on the data provided in the 1000 Genomes Project database. The aggregation addresses challenges from significant variability in the calling of CNV and SV boundaries and the need to consider frequency of variants with close boundaries in aggregation. For example, allele frequency of variants 1000–2000 CNV gain and 1005–2000 CNV gain are considered as a sum). Specifically:

• We selected alleles with 300 samples or more given the population group in the 1000 Genomes Project.

• We aggregated alleles based on their similarity defined by the reciprocal overlap being equal or exceeding 0.75.

• We calculated the aggregate frequency as the sum of all allele frequencies of the similar CNVs per given population group.

❗ The population frequency filter is only selectable in a filter group with a single selected variant category, as the population frequencies are tied to specific variant categories. The filter is not available for RNA Splice Variants and RNA Fusion Variants.

❗ The population frequency for copy number variants and structural variants is not displayed for alleles found in fewer than 300 samples per given population group in the 1000 Genomes Project.