BCOR c.4874+4A>C, p.?
NM_017745.5:c.4874+4A>C
Population Frequency
0.0 in 100,000
Rare
ClinVar Classification
Unknown
0 publications
REVEL Score
N/A
Not Available
COSMIC Recurrence
0 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
BCOR
Transcript
NM_017745.5
Total Exons
15
Strand
Reverse (−)
Reference Sequence
NC_000023.10
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_017745.6 | Alternative | 15 exons | Reverse |
| NM_017745.4 | Alternative | 15 exons | Reverse |
Variant Details
HGVS Notation
NM_017745.5:c.4874+4A>C
Protein Change
?
Location
Exon 14
(Exon 14 of 15)
5'
Exon Structure (15 total)
3'
Functional Consequence
Loss of Function
Related Variants
Variant interpretation based on transcript NM_017745.5
Clinical Evidence
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications
0 publications
Clinical Statement
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Functional Studies
Summary
The BCOR 4874+4a>C variant has not been functionally characterized, and its biological significance remains unknown.
Computational Evidence
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria
PVS1
PVS1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PVS1 is: "Null variant in a gene where loss of function (LoF) is a known mechanism of disease (e.g., nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multi-exon deletion in a LoF gene)". The evidence for this variant shows: it is an intronic +4 variant, not a canonical ±1 or ±2 splice site or other null variant. Therefore, this criterion is not applied because the variant type does not meet PVS1 requirements.
PS1
PS1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PS1 is: "Same amino acid change as a known pathogenic variant but different nucleotide change". The evidence for this variant shows: no amino acid change is generated (intronic variant) and no matching pathogenic missense reported. Therefore, this criterion is not applied because there is no identical amino acid change.
PS2
PS2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PS2 is: "De novo (both maternity and paternity confirmed) in a patient with the disease and no family history". The evidence for this variant shows: de novo status not assessed. Therefore, this criterion is not applied because there is no confirmed de novo data.
PS3
PS3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PS3 is: "Well-established functional studies supportive of a damaging effect on the gene or gene product". The evidence for this variant shows: no functional studies have been performed. Therefore, this criterion is not applied due to lack of functional evidence.
PS4
PS4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PS4 is: "Prevalence in affected individuals significantly increased compared with controls". The evidence for this variant shows: no case-control or cohort data available. Therefore, this criterion is not applied because prevalence in affected individuals is unknown.
PM1
PM1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM1 is: "Located in a mutational hot spot or well-established functional domain without benign variation". The evidence for this variant shows: no information on localization in a mutational hot spot or domain. Therefore, this criterion is not applied because domain/context data are lacking.
PM2
PM2 (Moderate)
According to standard ACMG guidelines, the rule for PM2 is: "Absent from controls (or at extremely low frequency if recessive)". The evidence for this variant shows: MAF = 0% in gnomAD and absence from other population databases. Therefore, this criterion is applied at Moderate strength because the variant is absent from population controls.
PM3
PM3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM3 is: "Detected in trans with a pathogenic variant (for recessive disorders)". The evidence for this variant shows: no information on trans configuration with another variant. Therefore, this criterion is not applied because zygosity and trans data are unavailable.
PM4
PM4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM4 is: "Protein length changes due to in-frame deletions/insertions or stop-loss variants". The evidence for this variant shows: no change in protein length (intronic variant). Therefore, this criterion is not applied because there is no protein length alteration.
PM5
PM5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM5 is: "Novel missense change at an amino acid residue where a different pathogenic missense change has been seen". The evidence for this variant shows: variant is not a missense change. Therefore, this criterion is not applied because it does not create a novel missense.
PM6
PM6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PM6 is: "Assumed de novo, but without confirmation of paternity and maternity". The evidence for this variant shows: no de novo assessment performed. Therefore, this criterion is not applied because de novo status is unconfirmed.
PP1
PP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP1 is: "Co-segregation with disease in multiple affected family members". The evidence for this variant shows: no family segregation data available. Therefore, this criterion is not applied because segregation evidence is lacking.
PP2
PP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP2 is: "Missense variant in a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease". The evidence for this variant shows: variant is intronic, not missense. Therefore, this criterion is not applied because it is not a missense variant.
PP3
PP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP3 is: "Multiple lines of computational evidence support a deleterious effect on the gene/gene product (e.g., conservation, splicing impact)". The evidence for this variant shows: in silico predictions are inconclusive, SpliceAI score 0.49 suggests low likelihood of impactful splicing. Therefore, this criterion is not applied due to lack of consistent computational support.
PP4
PP4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP4 is: "Patient's phenotype or family history highly specific for a disease with a single genetic etiology". The evidence for this variant shows: no clinical phenotype or family history provided. Therefore, this criterion is not applied because phenotypic specificity cannot be assessed.
PP5
PP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for PP5 is: "Reputable source reports variant as pathogenic, but without accessible evidence". The evidence for this variant shows: no entries in ClinVar or other reputable sources. Therefore, this criterion is not applied because no such reports exist.
BA1
BA1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BA1 is: "Allele frequency is too high for the disorder (based on population data)". The evidence for this variant shows: MAF = 0% in population databases. Therefore, this criterion is not applied because allele frequency is not above threshold.
BS1
BS1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BS1 is: "Allele frequency is greater than expected for the disorder". The evidence for this variant shows: MAF = 0%, well below expected maximum. Therefore, this criterion is not applied because allele frequency does not exceed expected levels.
BS2
BS2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BS2 is: "Observed in healthy individuals with full penetrance expected at an early age". The evidence for this variant shows: no observations in healthy adult cohorts. Therefore, this criterion is not applied due to lack of healthy individual data.
BS3
BS3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BS3 is: "Well-established functional studies show no damaging effect on protein function or splicing". The evidence for this variant shows: no functional assays performed. Therefore, this criterion is not applied because functional impact data are unavailable.
BS4
BS4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BS4 is: "Lack of segregation in affected family members". The evidence for this variant shows: no segregation studies reported. Therefore, this criterion is not applied because segregation evidence is absent.
BP1
BP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP1 is: "Missense variant in a gene where only LoF causes disease". The evidence for this variant shows: intronic location, not missense. Therefore, this criterion is not applied.
BP2
BP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP2 is: "Observed in trans with a pathogenic variant for dominant disorders or in cis with a pathogenic variant". The evidence for this variant shows: no information on cis/trans configuration with other variants. Therefore, this criterion is not applied due to lack of allelic context.
BP3
BP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP3 is: "In-frame deletions/insertions in a repetitive region without known function". The evidence for this variant shows: not an in-frame indel. Therefore, this criterion is not applied.
BP4
BP4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP4 is: "Multiple lines of computational evidence suggest no impact". The evidence for this variant shows: computational predictions inconclusive. Therefore, this criterion is not applied.
BP5
BP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP5 is: "Variant found in a case with an alternate molecular basis for disease". The evidence for this variant shows: no such case context. Therefore, this criterion is not applied due to lack of alternate molecular findings.
BP6
BP6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP6 is: "Reputable source reports variant as benign, but without accessible evidence". The evidence for this variant shows: no benign reports in any database. Therefore, this criterion is not applied.
BP7
BP7 (Not Applied)
Strength Modified
According to standard ACMG guidelines, the rule for BP7 is: "Synonymous variant with no predicted impact on splicing". The evidence for this variant shows: variant is intronic, not synonymous. Therefore, this criterion is not applied.