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BCORc.4677C>TUncertain significance
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Variant interpretation report

BCOR c.4677C>T, p.(Asp1559=)

NM_017745.5:c.4677C>T NP_060215.4:p.(Asp1559=) View identifiers
Classification
Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About BCOR

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 1
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 1
BP7Supporting
BP7 · supporting

This is a synonymous BCOR variant, p.(Asp1559=), and SpliceAI predicts no significant splice impact with a max delta score of 0.00. Available evidence supports BP7.

Recorded classification: Uncertain significance

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP7 supporting; combination = 1 supporting benign, which maps to VUS.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1
gnomAD v2.1
Population frequency
54 / 1,206,535 alleles

gnomAD v4.1: 54 / 1,206,535 alleles. Recorded AF 4.47563e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.43843e-05; MAF= 0.00444%, 8/180244 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.46649e-05; MAF= 0.00747%, 6/80359 alleles, homozygotes = 0); grpmax FAF= 3.178e-05.

No listed criterion applied
gnomAD v4.1 ↗gnomAD v2.1 ↗
No screenshot for this evidence
Computational predictions
Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

Applied · BP7 →
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed

No COSMIC evidence statement is recorded in this case.

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

28 criteria with recorded statuses: 1 met · 6 not met · 14 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The BCOR c.4677C>T (p.Asp1559=) variant has been reported in ClinVar with benign and likely benign classifications from two single submitters.

This variant is present in gnomAD v2.1 and v4.1 at low frequency (0.00444%-0.00448%), which is below the default BS1 threshold of 0.3% and BA1 threshold of 1.0%, so population frequency alone does not establish a stand-alone or strong benign criterion.

SpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.00, supporting a benign splicing interpretation consistent with BP7.

Cancer Hotspots did not identify a statistically significant hotspot at BCOR codon 1559, which does not support PM1.

Met · 1

BP7 SupportingThis is a synonymous BCOR variant, p.(Asp1559=), and SpliceAI predicts no significant splice impact with a max delta score of 0.00. Available evidence supports BP7. Details ▾Hide ▴
Evidence considered
  • Synonymous protein consequence p.(Asp1559=).
  • SpliceAI max delta score 0.00.
Still missing
  • No RNA study for this exact variant was identified.
Sources
spliceai ↗

Not met · 6 · evaluated, threshold not reached

PVS1 BCOR loss of function is an established disease mechanism at the gene level, but this variant is a synonymous change, p.(Asp1559=), outside the default generic PVS1 null-variant categories and SpliceAI predicts no significant splice effect (max delta score 0.00). Available evidence does not support applying PVS1. Details ▾Hide ▴
Rule
Generic PVS1 fallback withheld because the variant is not a nonsense, frameshift, or canonical +/-1,2 splice variant and no splice-disrupting evidence was identified.
Evidence considered
  • Gene-level BCOR loss-of-function mechanism is supported for generic PVS1 eligibility.
  • Variant-level PVS1 scaffold classifies this synonymous change outside the default null-variant buckets.
  • SpliceAI max delta score is 0.00.
Still missing
  • No RNA study for this exact variant was identified.
Sources
pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗spliceai ↗
PM1 Cancer Hotspots did not identify this residue as a statistically significant hotspot, and no evidence was identified that codon 1559 lies in a well-established critical region without benign variation. PM1 is not met. Details ▾Hide ▴
Evidence considered
  • No hotspot row was identified for BCOR D1559.
Sources
hotspots ↗
PM2 This variant is present in gnomAD v2.1 at 0.00444% (8/180244 alleles) and in gnomAD v4.1 at 0.00448% (54/1206535 alleles). Although both values are below the default 0.1% rarity threshold, the variant is not absent from population databases, so PM2 is not applied. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 AF 4.43843e-05.
  • gnomAD v4.1 AF 4.47563e-05.
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact with a max delta score of 0.00, and no REVEL or BayesDel score was available for this synonymous variant. PP3 is not met. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00.
  • REVEL not found.
  • BayesDel not found.
Still missing
  • No REVEL score was available.
  • No BayesDel score was available.
Sources
spliceai ↗
BA1 The highest observed population frequency is 0.00878% in gnomAD v4.1 Admixed American samples, which is below the 1.0% BA1 threshold. BA1 is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 highest subpopulation AF 8.78272e-05.
  • gnomAD v2.1 highest subpopulation AF 7.46649e-05.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 The highest observed population frequency is 0.00878% in gnomAD v4.1, which is below the default 0.3% BS1 threshold. BS1 is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 highest subpopulation AF 8.78272e-05.
  • gnomAD v2.1 highest subpopulation AF 7.46649e-05.
Sources
gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 14 · no assessment recorded

PS2 No confirmed de novo occurrence was identified for this variant, and no parental testing data were available. Details ▾Hide ▴
Evidence considered
  • No de novo evidence was retrieved.
Still missing
  • No case-level inheritance data were identified.
PS3 No published functional or RNA study for this exact variant was identified, so PS3 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • OncoKB did not provide variant-specific functional evidence.
Still missing
  • No variant-specific functional assay was identified.
  • No variant-specific RNA study was identified.
Sources
oncokb ↗
PS4 No enrichment data or repeated observations in affected individuals were identified for this variant, so PS4 is not established. Details ▾Hide ▴
Evidence considered
  • ClinVar contains limited submitter observations only.
  • The variant is present in population databases.
Still missing
  • No affected-vs-control enrichment data were identified.
  • No case series for this exact variant were identified.
Sources
clinvar ↗gnomad_v2 ↗gnomad_v4 ↗PMID:28492532 ↗
PM3 No allelic phase data or recessive case observations were identified for this variant, so PM3 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No phase data were retrieved.
Still missing
  • No trans observations were identified.
PM6 No assumed de novo report was identified for this variant, so PM6 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No de novo evidence was retrieved.
Still missing
  • No case-level inheritance information was identified.
PP1 No segregation data were identified for this variant, so PP1 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No segregation evidence was retrieved.
Still missing
  • No pedigree or co-segregation data were identified.
PP4 No phenotype-specific clinical data were provided to determine whether the observed features are highly specific for a BCOR-related disorder. Details ▾Hide ▴
Evidence considered
  • Phenotype data were not available in the reviewed materials.
Still missing
  • No phenotype or family history details were available.
PP5 Although ClinVar includes submissions for this variant, PP5 was not applied because submitter assertions alone were not used as independent pathogenic evidence. Details ▾Hide ▴
Evidence considered
  • ClinVar contains benign and likely benign submitter classifications.
Sources
clinvar ↗PMID:28492532 ↗
BS2 Population database observations alone do not establish that this variant is seen in clearly unaffected individuals at a level sufficient for BS2, so BS2 was not applied. Details ▾Hide ▴
Evidence considered
  • The variant is present at low frequency in gnomAD without homozygotes.
Still missing
  • No unaffected carrier evidence was identified.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No well-established functional or RNA study showing no damaging effect was identified for this variant, so BS3 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No variant-specific functional evidence was retrieved.
Still missing
  • No benign functional assay was identified.
  • No benign RNA study was identified.
Sources
oncokb ↗
BS4 No non-segregation data were identified for this variant, so BS4 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No family segregation data were retrieved.
Still missing
  • No family data showing lack of segregation were identified.
BP2 No phase data or alternate pathogenic variant data were identified, so BP2 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No phase data were retrieved.
Still missing
  • No cis/trans information was identified.
BP5 No evidence was identified for an alternate molecular explanation for disease, so BP5 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • No alternate molecular explanation was retrieved.
Still missing
  • No alternate molecular diagnosis was provided.
BP6 ClinVar includes benign and likely benign classifications for this variant, but BP6 was not applied because submitter assertions alone were not used as independent benign evidence. Details ▾Hide ▴
Evidence considered
  • ClinVar reports one benign and one likely benign single-submitter classification.
Sources
clinvar ↗PMID:28492532 ↗
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to a different nucleotide change that results in the same amino acid change as an established pathogenic variant. This variant is synonymous and no such pathogenic comparison was identified. Details ▾Hide ▴
Evidence considered
  • Protein consequence is p.(Asp1559=).
PM4 N/APM4 applies to protein length changes from in-frame insertions, deletions, or stop-loss variants. This variant is synonymous and does not alter protein length. Details ▾Hide ▴
Evidence considered
  • Protein consequence is p.(Asp1559=).
PM5 N/APM5 applies to a novel missense change at a residue where another pathogenic missense change has been established. This variant is not a missense change. Details ▾Hide ▴
Evidence considered
  • Protein consequence is p.(Asp1559=).
PP2 N/APP2 is used for missense variants in genes with a low rate of benign missense variation and a common pathogenic missense mechanism. This variant is synonymous. Details ▾Hide ▴
Evidence considered
  • Protein consequence is p.(Asp1559=).
BP1 N/ABP1 applies to missense variants in genes where truncating variants are primarily pathogenic. This variant is synonymous. Details ▾Hide ▴
Evidence considered
  • Protein consequence is p.(Asp1559=).
BP3 N/ABP3 applies to in-frame insertions or deletions in repetitive regions without known function. This variant is a synonymous substitution. Details ▾Hide ▴
Evidence considered
  • Variant type is synonymous substitution.
BP4 N/AFor this synonymous variant, the relevant benign computational assessment is captured under BP7. REVEL and BayesDel were not available, and no separate BP4 assessment was applied. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00.
  • REVEL not found.
  • BayesDel not found.
Still missing
  • No REVEL score was available.
  • No BayesDel score was available.
Sources
spliceai ↗

Identifiers

Gene
BCOR
Transcript
NM_017745.5
Coding (HGVS c.)
NM_017745.5:c.4677C>T
Protein (HGVS p.)
NP_060215.4:p.(Asp1559=)
GRCh38
chrX:40054296 G>A
GRCh37
chrX:39913549 G>A

Gene diagram

Every interpreted variant in BCOR, mapped onto the exon structure of NM_017745.5. Select a row to find it on the plot.

BCORNM_017745.5
Fetching transcript structure from UCSC…
gnomAD v4.1 54 / 1,206,535 alleles AF 4.48e-05 · 0 homozygotes · FAF 3.95e-05
gnomAD v2.1 8 / 180,244 alleles AF 4.44e-05 · 0 homozygotes · FAF 3.18e-05

By genetic ancestry

gnomAD v4.1

AF 4.5e-05 · 54 / 1,206,535 alleles · 0 hom · FAF 3.9e-05
Admixed American4 / 45,544 8.8e-05
European (non-Finnish)46 / 892,975 5.2e-05
Remaining individuals2 / 47,508 4.2e-05
African/African American2 / 56,928 3.5e-05
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 4.4e-05 · 8 / 180,244 alleles · 0 hom · FAF 3.2e-05
European (non-Finnish)6 / 80,359 7.5e-05
Admixed American2 / 27,190 7.4e-05
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 4.47563e-05; MAF= 0.00448%, 54/1206535 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.78272e-05; MAF= 0.00878%, 4/45544 alleles, homozygotes = 0); grpmax FAF= 3.948e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.43843e-05; MAF= 0.00444%, 8/180244 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.46649e-05; MAF= 0.00747%, 6/80359 alleles, homozygotes = 0); grpmax FAF= 3.178e-05.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP7 SupportingThis is a synonymous BCOR variant, p.(Asp1559=), and SpliceAI predicts no significant splice impact with a max delta score of 0.00. Available evidence supports BP7. Details ▾Hide ▴
Evidence considered
  • Synonymous protein consequence p.(Asp1559=).
  • SpliceAI max delta score 0.00.
Still missing
  • No RNA study for this exact variant was identified.
Sources
spliceai ↗
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact with a max delta score of 0.00, and no REVEL or BayesDel score was available for this synonymous variant. PP3 is not met. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00.
  • REVEL not found.
  • BayesDel not found.
Still missing
  • No REVEL score was available.
  • No BayesDel score was available.
Sources
spliceai ↗
BP4 N/AFor this synonymous variant, the relevant benign computational assessment is captured under BP7. REVEL and BayesDel were not available, and no separate BP4 assessment was applied. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.00.
  • REVEL not found.
  • BayesDel not found.
Still missing
  • No REVEL score was available.
  • No BayesDel score was available.
Sources
spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 54 / 1,206,535 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Captured SpliceAI source record Open source ↗
ClinVar Captured ClinVar source record Open source ↗
COSMIC Captured COSMIC source record Open source ↗
Cancer hotspots Captured Cancer Hotspots source record Open source ↗
OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 4.47563e-05; MAF= 0.00448%, 54/1206535 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.78272e-05; MAF= 0.00878%, 4/45544 alleles, homozygotes = 0); grpmax FAF= 3.948e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.43843e-05; MAF= 0.00444%, 8/180244 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.46649e-05; MAF= 0.00747%, 6/80359 alleles, homozygotes = 0); grpmax FAF= 3.178e-05.

ClinVar

This variant has been reported in ClinVar as Benign (1 clinical laboratory) and as Likely benign (1 clinical laboratory).

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.