Genomic Filtering

PIC-SURE allows you to add genomic filters to refine your cohort. There are two main ways to add a genomic filter: using gene names or specific single nucleotide polymorphisms (SNPs).

Two genomic filtering options: Variants by gene name or Specific SNPs

Variants by Gene Name

With this option, you can select options from the following fields:

• Gene with Variant: Search and select the gene name(s) using the official gene symbol that contains the variant of interest.

• Calculated Consequence: Select the desired calculated consequences based on VEP annotation. The consequences are organized by high, medium, and low severity. The listed consequences are standardized terms from the Sequence Ontology (http://www.sequenceontology.org) that describe the calculated consequence of a variant. The severity for the calculated consequence of a variant on a gene has possible values HIGH (frameshift, splice disrupting, or truncating variants), MEDIUM (non-frameshift insertions or deletions, variants altering protein sequencing without affecting its length) or LOW (other coding variants including synonymous variants).

• Variant Frequency: Displayed variant frequencies are based on the gnomAD combined population as discrete text categories. Possible values: Novel (variant not in gnomAD database), Rare (variant frequency less than 1%), Common (variant frequency greater than or equal to 1%).

Not all options need to have a selection made, but it does help to narrow down the cohort if one or more genes with variants are selected.

Gene with Variant filtering options selecting BRCA1 rare variants with stop gained, frameshift, stop lost, and start lost consequences.

Specific SNPs

This option allows you to select specific SNPs based on chromosomal location. To use this option, you will need to know the chromosome, position, and reference and alternate alleles. The search accepts this format: chr<NUMBER>,<POSITION NUMBER>,<REF ALLELE>,<ALT ALLELE>

For example, chr5,148481541,T,A

Please note that the SNP may not exist in the database.

Once you've searched for a SNP, you will be able to select from the following options: Heterozygous, Homozygous, Heterozygous or Homozygous, or Exclude Variant.