owencqueen/cgbench_data huggingface dataset:
Gene: ANO5 (HGNC:27337)
Evidence Code: PP4 — Original ACMG Summary
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
Gene: ANO5 (HGNC:27337)
Evidence Code: PP4 — Supporting
Modification Type: Disease-specific
Apply PP4 (Supporting) for a proband meeting both of the following criteria:




progressive limb-girdle pattern of muscle weakness observed over ≥6 mo OR clinical suspicion of LGMD
1


2 presumed diagnostic variants in 
ANO5
, 1 of which is the variant under curation
2




1
 May be accompanied by supporting EMG, MRI, muscle histology, elevated CK but not required.


2
 Screening of all exons and exon/intron boundaries of 
ANO5
 required. Screening of additional neuromuscular disease genes (e.g., through a panel) is recommended but not required. If variants have not yet been curated by the LGMD VCEP, confirm they cannot be classified as LB or B (e.g., through application of BA1, BS1, and/or BP4/BP7). If phase is unknown, do not apply if the identified variants were ever confirmed 
in cis
 or if gnomAD co-occurrence data (
https://gnomad.broadinstitute.org/variant-cooccurrence
) predict the variants may be part of the same haplotype in at least one genetic ancestry group.
Gene: ANO5 (HGNC:27337)
Evidence Code: PP5 — Original ACMG Summary
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: ANO5 (HGNC:27337)
Evidence Code: BA1 — Original ACMG Summary
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
Gene: ANO5 (HGNC:27337)
Evidence Code: BA1 — Stand Alone
Modification Type: Disease-specific
Apply if the variant Grpmax FAF (the lower bound of the 95% confidence interval of the maximum credible genetic ancestry group allele frequency) is >0.003. This value can be taken directly from gnomAD. See supplementary file “benign frequency exceptions” for a list of variants defined as exceptions to the benign frequency rules. Ongoing updates to this list will be available at the LGMD VCEP webpage: 
https://clinicalgenome.org/affiliation/50061/.
 Variants whose frequency may not be reliable (e.g., variants that may reflect a sequencing artifact) should be critically evaluated and brought to the attention of the LGMD VCEP.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS1 — Original ACMG Summary
Allele frequency is greater than expected for disorder.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS1 — Strong
Modification Type: Disease-specific
Apply if the variant Grpmax FAF (the lower bound of the 95% confidence interval of the maximum credible genetic ancestry group allele frequency) is >0.001. This value can be taken directly from gnomAD. See supplementary file “benign frequency exceptions” for a list of variants defined as exceptions to the benign frequency rules. Ongoing updates to this list will be available at the LGMD VCEP webpage: 
https://clinicalgenome.org/affiliation/50061/.
 Variants whose frequency may not be reliable (e.g., variants that may reflect a sequencing artifact) should be critically evaluated and brought to the attention of the LGMD VCEP.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS2 — Original ACMG Summary
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS3 — Original ACMG Summary
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS4 — Original ACMG Summary
Lack of segregation in affected members of a family.
Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals. Also, families may have more than one pathogenic variant contributing to an autosomal dominant disorder, further confounding an apparent lack of segregation.
Gene: ANO5 (HGNC:27337)
Evidence Code: BS4 — Strong
Modification Type: Clarification
Use as is. One affected individual (genotype-, phenotype+) is sufficient for BS4. Do not apply for genotype+, phenotype- individuals, as LGMD is characterized by variable expressivity and late onset is not uncommon.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP1 — Original ACMG Summary
Missense variant in a gene for which primarily truncating variants are known to cause disease.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP2 — Original ACMG Summary
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP2 — Supporting
Modification Type: Disease-specific
Use when variant is found 
in cis
 with a variant classified as pathogenic or likely pathogenic using the LGMD VCEP specifications.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP3 — Original ACMG Summary
In frame-deletions/insertions in a repetitive region without a known function.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP4 — Original ACMG Summary
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm cannot be counted as an independent criterion. BP4 can be used only once in any evaluation of a variant.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP4 — Supporting
Modification Type: Disease-specific
For missense variants, use REVEL with a score ≤0.1 AND SpliceAI with a score ≤0.05.


For variants that may affect splicing, use SpliceAI with a score ≤0.05.


Splice AI scores can be calculated here: 
https://spliceailookup.broadinstitute.org/
Gene: ANO5 (HGNC:27337)
Evidence Code: BP5 — Original ACMG Summary
Variant found in a case with an alternate molecular basis for disease.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP6 — Original ACMG Summary
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP7 — Original ACMG Summary
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Gene: ANO5 (HGNC:27337)
Evidence Code: BP7 — Supporting
Modification Type: Disease-specific
For splice predictions, use SpliceAI with a score ≤0.05. BP7 may be co-applied with BP4 for synonymous, UTR, and intronic variants located outside the splice donor/acceptor regions designated in Walker et al. 2023 (+7/-21).