owencqueen/cgbench_data huggingface dataset:
Gene: TP53 (HGNC:11998)
Evidence Code: PM2 — Supporting
Modification Type: Disease-specific,General recommendation
This rule should be applied at supporting level. Variant should have an allele frequency of less than 0.00003 (0.003%) in gnomAD or another large sequenced population. If multiple alleles are present within any genetic ancestry group, allele frequency in that group must be <0.00004 (0.004%). Genetic ancestry groups influenced by founder effects (such as Ashkenazi Jewish, Finnish, Amish, Middle Eastern, and “Remaining”) should be ignored. 


If the variant being assessed does not meet any population rule codes (PM2, BA1, BS1) 
AND
 has a total allele frequency >0.00003 with no single genetic ancestry group having multiple alleles with a frequency >0.00004, curators should recalculate the total allele frequency based on the number of alleles with variant allele fraction (VAF) >0.35 to assess whether PM2 may be met after excluding the low VAF alleles which are likely to represent clonal hematopoiesis of indeterminant potential (CHIP) contamination in the database. This can be done by visualizing the “allele balance” for heterozygotes under the genotype quality metrics for a given variant. By hovering over the histogram bars, the number of variant carriers for each bar between 0.35 and 0.65 can be totaled and this can be used to revise the allele count to determine the allele frequency that can be used to assess if PM2_Supporting can be met.


In general, the most recent version of gnomAD should be used when available; however, other population databases or earlier versions of gnomAD may be utilized if they are able to provide information the curator deems necessary for optimal variant classification (e.g, they would provide superior information for a particular variant type; have a larger sample size; or better representation for certain subpopulations, etc.)
Gene: TP53 (HGNC:11998)
Evidence Code: PP4 — Supporting
Modification Type: Disease-specific,Strength
Observation of the variant with VAF 5-35% (i.e., once or multiple times with VAF >25-35% and/or once with VAF 5-25%)
Gene: TP53 (HGNC:11998)
Evidence Code: BP7 — Strong
Modification Type: Disease-specific
A (synonymous) silent or intronic variant for which RNA splicing assay data demonstrates no splicing aberration, as per recommendations from Walker et al., 2023 (PMID: 37352859).