About BCOR
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BCOR c.519C>T, p.(Ser173=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
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: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP6Supporting
BP6 · supporting
Three independent clinical laboratories classify this variant as Likely Benign in ClinVar (Labcorp/Invitae SCV002392005, PreventionGenetics SCV004781451, CeGaT SCV004164852). While these are single-submitter assertions without expert panel review, the consistent direction across multiple clinical testing laboratories provides supporting evidence for a benign assessment.
BP7Supporting
BP7 · supporting
Synonymous variant (p.Ser173=) with SpliceAI delta score of 0.00 across all categories (donor gain 0.00, donor loss 0.00, acceptor gain 0.00, acceptor loss 0.00), predicting no impact on splicing. The variant does not affect the splice consensus sequence nor create a novel splice site.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP6 supporting benign, BP7 supporting benign; combination = 2 supporting benign, which maps to Likely Benign.
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
424 / 1,209,884 alleles
gnomAD v4.1: 424 / 1,209,884 alleles. Recorded AF 0.000350447. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000165827; MAF= 0.01658%, 34/205033 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000281187; MAF= 0.02812%, 26/92465 alleles, homozygotes = 0); grpmax FAF= 0.00021222.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV60708452, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 19 not met · 1 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_017745.5:c.519C>T is a synonymous variant (p.Ser173=) in exon 4 of BCOR that does not alter the protein sequence.
SpliceAI predicts no impact on splicing (max delta score 0.00), consistent with BP7 (Supporting Benign).
Three clinical laboratories in ClinVar classify this variant as Likely Benign, consistent with BP6 (Supporting Benign).
The variant is observed in gnomAD at 0.035% in v4.1 (424 alleles) with no homozygotes, which is below the PM2 threshold of 0.1% but also below the BS1 threshold of 0.3%; population frequency is uninformative for this synonymous variant.
No pathogenic or likely pathogenic ClinVar submissions, no functional evidence of damaging effect, and no segregation, de novo, or case-control data were identified to support a pathogenic classification.
No criteria match.
Met · 2
BP6 SupportingThree independent clinical laboratories classify this variant as Likely Benign in ClinVar (Labcorp/Invitae SCV002392005, PreventionGenetics SCV004781451, CeGaT SCV004164852). While these are single-submitter assertions without expert panel review, the consistent direction across multiple clinical testing laboratories provides supporting evidence for a benign assessment. Details ▾Hide ▴
Evidence considered
- Labcorp/Invitae (SCV002392005): Likely Benign
- criteria provided
- PreventionGenetics (SCV004781451): Likely Benign
- CeGaT (SCV004164852): Likely Benign
Still missing
- No expert panel classification available
- Individual lab criteria not publicly accessible for independent verification
Sources
BP7 SupportingSynonymous variant (p.Ser173=) with SpliceAI delta score of 0.00 across all categories (donor gain 0.00, donor loss 0.00, acceptor gain 0.00, acceptor loss 0.00), predicting no impact on splicing. The variant does not affect the splice consensus sequence nor create a novel splice site. Details ▾Hide ▴
Evidence considered
- Synonymous substitution c.519C>T → p.(Ser173=)
- SpliceAI max delta 0.00 — no predicted donor/acceptor gain or loss
- No alteration to canonical splice site motifs
Still missing
- Nucleotide conservation at c.519 not explicitly assessed — BP7 also requires the nucleotide not be highly conserved
- though this is secondary to the SpliceAI prediction
Sources
Not met · 19 · evaluated, threshold not reached
PS2 No de novo evidence identified in ClinVar submissions, literature review, or population data. No family studies reporting de novo occurrence of this variant were found. Details ▾Hide ▴
Evidence considered
- ClinVar submissions show no de novo origin claims
- No publications with de novo data identified
Still missing
- No parental testing data available
Sources
PS3 No functional studies demonstrating a damaging effect on the gene or gene product have been identified. The sole literature PMID (25741868) is the ACMG/AMP guidelines document and contains no variant-specific functional data. OncoKB lists oncogenicity as 'Unknown Oncogenic Effect' with no supporting functional publications. Details ▾Hide ▴
Evidence considered
- No variant-specific functional studies identified
- OncoKB: Unknown Oncogenic Effect
- REVEL/BayesDel scores unavailable for this variant
Still missing
- No functional assays performed for this variant
- No in silico protein-level scores available (REVEL/BayesDel not found)
Sources
PS4 No case-control enrichment data or statistically significant excess of variant in affected individuals versus controls. The variant is observed in gnomAD at 0.017-0.035% (34-424 alleles), consistent with a population polymorphism rather than a disease-associated variant. No clinical series or cohort studies comparing affected vs. control prevalence were identified. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 34/205
- 033 alleles (AF 0.017%)
- gnomAD v4.1: 424/1
- 209
- 884 alleles (AF 0.035%)
- ClinVar: 3 Likely Benign
- 1 VUS — no pathogenic consensus
Still missing
- No case-control study for BCOR c.519C>T
Sources
PM1 This synonymous variant is located in exon 4 of BCOR (c.519). It does not lie within a recognized mutational hotspot or a critical, well-established functional domain without benign variation. The hotspots analysis confirms no statistically significant hotspot at this residue and no enrichment at this position. Details ▾Hide ▴
Evidence considered
- Hotspot residue not significant
- Exact variant not listed in cancer hotspots
- No established BCOR critical domain at this position
PM2 The variant is present in gnomAD with 34 alleles in v2.1 (AF 0.017%) and 424 alleles in v4.1 (AF 0.035%). While below the generic 0.1% PM2 threshold, the observation of 424 alleles in a general population database for a synonymous variant on the X chromosome is not consistent with a rare pathogenic variant. PM2 is not applied. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF 0.0166%
- 34/205
- 033 alleles
- 0 homozygotes
- gnomAD v4.1: AF 0.0350%
- 424/1
- 209
- 884 alleles
Sources
PM6 No de novo occurrence (with maternity and paternity confirmed) has been reported for this variant in the reviewed literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No de novo reports with confirmed parentage in ClinVar or literature
Still missing
- No parental testing data available
Sources
PP1 No cosegregation data available. No family studies demonstrating segregation of this variant with a BCOR-related phenotype were identified in the literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No family segregation data identified
Still missing
- No family studies available
Sources
PP2 BCOR is not established as a gene with a low rate of benign missense variation where missense changes are a common mechanism of disease. Furthermore, this is a synonymous variant; PP2 specifically addresses missense variant constraint. Details ▾Hide ▴
Evidence considered
- BCOR is not on the standard PP2 gene list
- Synonymous variant does not fit PP2 missense framework
PP3 No in silico evidence supports a pathogenic effect. REVEL and BayesDel scores are unavailable for this variant. SpliceAI predicts no splicing impact (max delta = 0.00). Multiple in silico tools are not available to support pathogenicity. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.00 — no predicted splice impact
- REVEL not found
- BayesDel not found
- HCI prior not found (gene not supported)
Still missing
- REVEL and BayesDel scores unavailable for chrX
Sources
PP4 No patient phenotype data specific to a BCOR-related disorder is available for review. The ClinVar submissions list 'not specified' or 'BCOR-related condition' as indications, and no detailed clinical phenotype is described that is highly specific for BCOR-related disease. Details ▾Hide ▴
Evidence considered
- ClinVar condition labels: 'not specified'
- 'BCOR-related condition'
- No detailed phenotype data available
Still missing
- No patient-specific phenotype data available
Sources
PP5 No reputable source classifies this variant as pathogenic. In ClinVar, three clinical laboratories classify this variant as Likely Benign (Labcorp/Invitae, PreventionGenetics, CeGaT) and one classifies it as Uncertain Significance (University of Chicago). No expert panel or strong diagnostic laboratory has asserted pathogenicity. Details ▾Hide ▴
Evidence considered
- ClinVar: 3 Likely Benign
- 1 Uncertain Significance
- No pathogenic assertion from any clinical laboratory or expert panel
Sources
BA1 Maximum population allele frequency is 0.043% (NFE in gnomAD v4.1), well below the 1% BA1 threshold. This variant is not common enough to be considered a benign polymorphism by allele frequency alone. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 max subpop AF: 0.0430% (NFE)
- gnomAD v2.1 max subpop AF: 0.0281% (NFE)
- Both well below 1% BA1 threshold
Sources
BS1 Maximum population allele frequency is 0.043% (NFE in gnomAD v4.1), below the 0.3% BS1 threshold for non-VCEP assessment. The variant is not sufficiently common in the general population to meet BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 max subpop AF: 0.0430% (NFE)
- gnomAD v2.1 max subpop AF: 0.0281% (NFE)
- Both below 0.3% BS1 threshold
Sources
BS2 No homozygous observations in gnomAD (0 homozygotes across v2.1 and v4.1). BCOR is on chromosome X, further complicating homozygosity interpretation. No evidence of this variant observed in a healthy adult in a homozygous state, or in trans with a pathogenic variant. Details ▾Hide ▴
Evidence considered
- 0 homozygotes in gnomAD v2.1 and v4.1
- X-linked gene limits homozygosity expectations
Still missing
- No observations in trans with pathogenic BCOR variants
Sources
BS3 No functional studies demonstrating no deleterious effect have been identified. The reviewed literature (PMID:25741868) is a methodological guidelines document and contains no variant-specific functional data. While SpliceAI predicts no splicing impact, a single in silico prediction tool is insufficient to meet BS3 threshold. Details ▾Hide ▴
Evidence considered
- No variant-specific functional assays identified
- SpliceAI delta 0.00 consistent with no splice effect but alone insufficient for BS3
Still missing
- No experimental functional studies available
Sources
BS4 No segregation data demonstrating lack of cosegregation with disease in affected family members. No families with discordant segregation patterns have been identified. Details ▾Hide ▴
Evidence considered
- No family segregation data available
Still missing
- No family studies available
BP2 No evidence of this variant observed in trans with a known pathogenic BCOR variant. No phase data available from ClinVar submissions or literature. Details ▾Hide ▴
Evidence considered
- No trans observations in ClinVar or literature
Still missing
- No phase data available
Sources
BP4 Insufficient multiple lines of computational evidence to classify as benign. While SpliceAI predicts no splice impact (delta 0.00), REVEL and BayesDel scores are unavailable. A single neutral in silico score does not constitute multiple lines of evidence for BP4. BP7 is the more appropriate criterion for a synonymous variant with a benign splicing prediction. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.00 — no predicted splice impact
- REVEL not found
- BayesDel not found
Still missing
- No REVEL or BayesDel scores available
- Single tool insufficient for BP4 multiple-lines requirement
Sources
BP5 No case reports identifying this variant in an individual with an alternative molecular basis for disease have been identified. No evidence of a different pathogenic variant explaining the phenotype in a carrier of this variant. Details ▾Hide ▴
Evidence considered
- No case reports with alternative molecular diagnosis identified
Still missing
- No case-level data available for review
Not assessed · 1 · no assessment recorded
PS5 Insufficient evidence to assess PS5. No new pathogenic de novo or functional evidence has emerged that has not already been evaluated under PS2 and PS3. Details ▾Hide ▴
Evidence considered
- No novel evidence beyond PS2/PS3 scope identified
Still missing
- No new data sources identified
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ASynonymous variant (p.Ser173=) with no predicted null effect on the protein. The ClinGen SVI PVS1 decision tree does not apply to synonymous variants that do not affect splicing; variant_bucket is 'other'. Details ▾Hide ▴
Evidence considered
- Synonymous substitution NM_017745.5:c.519C>T resulting in p.(Ser173=)
- SpliceAI max delta 0.00 confirms no splice impact
- Variant does not fall into PVS1 null-variant buckets (nonsense
- frameshift
- canonical ±1
- 2 splice)
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PS1 N/ASynonymous variant; PS1 requires a different nucleotide change at the same amino acid position that is known to be pathogenic. A synonymous change with no amino acid alteration cannot meet PS1 semantics. Details ▾Hide ▴
Evidence considered
- p.(Ser173=) is synonymous
- no amino acid change
PM5 N/ASynonymous variant (p.Ser173=); PM5 requires a different amino acid change at the same residue that is known to be pathogenic. With no amino acid change, same-residue comparator analysis is not applicable. Details ▾Hide ▴
Evidence considered
- p.(Ser173=) is synonymous — no amino acid change for residue comparison
- pm5_candidates: eligible_for_classic_pm5_search is false
Sources
pm5_candidates
BP1 N/ASynonymous variant; BP1 applies specifically to missense variants where a different missense at the same position is known to be benign and the gene mechanism is truncating. Not applicable to synonymous changes. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Ser173=)
- BP1 addresses missense variants
Identifiers
- Gene
- BCOR
- Transcript
- NM_017745.5
- Coding (HGVS c.)
- NM_017745.5:c.519C>T
- Protein (HGVS p.)
- NP_060215.4:p.(Ser173=)
- GRCh38
- chrX:40074827 G>A
- GRCh37
- chrX:39934080 G>A
- ClinVar
- 210524
- COSMIC
- COSV60708452
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…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in BCOR
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
424 / 1,209,884 alleles
AF 0.00035 · 0 homozygotes · FAF 0.000394
gnomAD v2.1
34 / 205,033 alleles
AF 0.000166 · 0 homozygotes · FAF 0.000212
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00035 · 424 / 1,209,884 alleles · 0 hom · FAF 0.00039
| European (non-Finnish)385 / 895,144 | 0.00043 |
| Remaining individuals17 / 47,603 | 0.00036 |
| South Asian16 / 56,768 | 0.00028 |
| Admixed American3 / 45,821 | 6.5e-05 |
| African/African American2 / 57,063 | 3.5e-05 |
| East Asian1 / 33,762 | 3e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00017 · 34 / 205,033 alleles · 0 hom · FAF 0.00021
| European (non-Finnish)26 / 92,465 | 0.00028 |
| South Asian4 / 19,080 | 0.00021 |
| Admixed American3 / 28,048 | 0.00011 |
| East Asian1 / 14,844 | 6.7e-05 |
0 alternate alleles recorded in 4 other groups: African/African American, Ashkenazi Jewish, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000350447; MAF= 0.03504%, 424/1209884 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000430098; MAF= 0.04301%, 385/895144 alleles, homozygotes = 0); grpmax FAF= 0.00039444.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000165827; MAF= 0.01658%, 34/205033 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000281187; MAF= 0.02812%, 26/92465 alleles, homozygotes = 0); grpmax FAF= 0.00021222.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP7 SupportingSynonymous variant (p.Ser173=) with SpliceAI delta score of 0.00 across all categories (donor gain 0.00, donor loss 0.00, acceptor gain 0.00, acceptor loss 0.00), predicting no impact on splicing. The variant does not affect the splice consensus sequence nor create a novel splice site. Details ▾Hide ▴
Evidence considered
- Synonymous substitution c.519C>T → p.(Ser173=)
- SpliceAI max delta 0.00 — no predicted donor/acceptor gain or loss
- No alteration to canonical splice site motifs
Still missing
- Nucleotide conservation at c.519 not explicitly assessed — BP7 also requires the nucleotide not be highly conserved
- though this is secondary to the SpliceAI prediction
Sources
PP3 No in silico evidence supports a pathogenic effect. REVEL and BayesDel scores are unavailable for this variant. SpliceAI predicts no splicing impact (max delta = 0.00). Multiple in silico tools are not available to support pathogenicity. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.00 — no predicted splice impact
- REVEL not found
- BayesDel not found
- HCI prior not found (gene not supported)
Still missing
- REVEL and BayesDel scores unavailable for chrX
Sources
BP4 Insufficient multiple lines of computational evidence to classify as benign. While SpliceAI predicts no splice impact (delta 0.00), REVEL and BayesDel scores are unavailable. A single neutral in silico score does not constitute multiple lines of evidence for BP4. BP7 is the more appropriate criterion for a synonymous variant with a benign splicing prediction. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.00 — no predicted splice impact
- REVEL not found
- BayesDel not found
Still missing
- No REVEL or BayesDel scores available
- Single tool insufficient for BP4 multiple-lines requirement
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
2 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015Richards et al. (2015) present the ACMG/AMP standards and guidelines for sequence variant interpretation. This is a methodological framework document. NM_017745.5:c.519C>T (BCOR) was not identified in this paper.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp et al. (2017) present Sherloc, a comprehensive refinement of the ACMG-AMP variant classification criteria. This is a methodological framework document. NM_017745.5:c.519C>T was not identified in the available metadata; full-text confirmation was not possible.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
424 / 1,209,884 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
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
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/210524/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/X-39934080-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chrX-40074827-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/X-40074827-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_017745.5%3Ac.519C…
- OncoKB ↗www.oncokb.org/gene/BCOR/S173=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=139471554
- Cancer hotspots ↗www.cancerhotspots.org/
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= 0.000350447; MAF= 0.03504%, 424/1209884 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000430098; MAF= 0.04301%, 385/895144 alleles, homozygotes = 0); grpmax FAF= 0.00039444.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000165827; MAF= 0.01658%, 34/205033 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000281187; MAF= 0.02812%, 26/92465 alleles, homozygotes = 0); grpmax FAF= 0.00021222.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant is present in ClinVar (Variation ID: 210524); submission details unavailable.
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 previously been reported in somatic cancers (COSMIC; COSV60708452, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.