owencqueen/cgbench_data huggingface dataset:
Gene: TCF4 (HGNC:11634)
Evidence Code: PVS1 — Very Strong
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




Use as defined by ClinGen SVI working group (PMID:30192042).


PVS1 can be applied for:


Null variants up to p.E643, which corresponds to the distal most de novo truncating variant in an affected patient reported to date.
4


Any frameshift variant that results in a read-through of the stop codon


Canonical splice site variants predicted to result in an out-of-frame product


Canonical splice site variants or single in-frame deletions predicted to preserve the reading frame (exon 15)


In-frame deletions including the PM1 functional domains (p.E564_V617 (bHLH))


Deletions and duplications ≥1 exon in size (that are completely contained within the 
TCF4
 gene) where the reading frame is disrupted and NMD is predicted to occur


Exon skipping or single exon deletion of exon 19 predicted to disrupt the reading frame but is not predicted to undergo NMD


A full gene deletion
Gene: TCF4 (HGNC:11634)
Evidence Code: PVS1 — Strong
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




PVS1_Strong is applicable for single to multi exon deletions that preserve the reading frame and the variant removes <10% of the protein.
Gene: TCF4 (HGNC:11634)
Evidence Code: PP3 — Supporting
Modification Type: Clarification
Multiple lines of computational evidence support a deleterious effect on the gene or gene product.




For missense variants use REVEL with a score ≥ 0.644.


For splice site variants use SpliceAI with a score ≥ 0.2.
Gene: TCF4 (HGNC:11634)
Evidence Code: BS3 — Strong
Modification Type: Disease-specific
Well-established in vitro or in vivo functional studies shows no damaging effect on protein function.




RNA functional studies that demonstrate no impact on splicing and transcript composition. It can be downgraded based on quality of data.


Not applicable for other functional studies.
Gene: TCF4 (HGNC:11634)
Evidence Code: BP3 — Supporting
Modification Type: None
In-frame deletions/insertions in a repetitive region without a known function.




BP3 is applicable if there are in-frame deletions/duplications in a repetitive region where other in-frame deletions/duplications have been observed with an overall frequency commensurate with the BA1 threshold for this gene.
Gene: TCF4 (HGNC:11634)
Evidence Code: BP4 — Supporting
Modification Type: General recommendation
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)




For missense variants use REVEL with a score ≤ 0.290.


For splice site variants use SpliceAI with a score ≤ 0.1.
Gene: TCF4 (HGNC:11634)
Evidence Code: BP5 — Moderate
Modification Type: Strength
Variant found in a case with an alternate molecular basis for disease.




2 cases with alternate molecular basis for disease.
Gene: TCF4 (HGNC:11634)
Evidence Code: BP5 — Supporting
Modification Type: Disease-specific
Variant found in a case with an alternate molecular basis for disease.




1 case with alternate molecular basis for disease.
Gene: TCF4 (HGNC:11634)
Evidence Code: BP7 — Supporting
Modification Type: None
A synonymous (silent) 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.




Defined 'not highly conserved' regions in BP7 as those with PhastCons score <1 and/or PhyloP score <0.1 and/or the variant is the reference nucleotide in one primate and/or three mammal species.


For splice site variants use SpliceAI with a score ≤ 0.1.