About BCORL1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BCORL1 c.4464C>T, p.(Asp1488=)
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.
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present at low frequency in population databases. In gnomAD v2.1 the overall AF is 0.00396% and in gnomAD v4.1 the overall AF is 0.00399%; the highest observed subpopulation frequency in gnomAD v4.1 is 0.04636%, which is below the 0.1% threshold used here for PM2.
Benign criteria applied · 1
BP7Supporting
BP7 · supporting
This is a synonymous variant, p.(Asp1488=), and available computational evidence predicts no significant effect on splicing. SpliceAI shows a maximum delta score of 0.01, and the variant-level splice assessment indicates that it is not in a canonical splice consensus position, supporting 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: PM2 supporting, BP7 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.
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
48 / 1,203,445 alleles
gnomAD v4.1: 48 / 1,203,445 alleles. Recorded AF 3.98855e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.95514e-05; MAF= 0.00396%, 7/176985 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000169367; MAF= 0.01694%, 3/17713 alleles, homozygotes = 0); grpmax FAF= 4.577e-05.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
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
5 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV54397317, n = 5 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.
28 criteria with recorded statuses: 2 met · 5 not met · 14 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BCORL1 NM_021946.4:c.4464C>T (p.Asp1488=) variant has not been reported in ClinVar.
This variant is present at low frequency in gnomAD, with overall allele frequencies of 0.00396% in v2.1 and 0.00399% in v4.1; the highest observed subpopulation frequency is 0.04636% in gnomAD v4.1, which is below the 0.1% PM2 threshold and below the 0.3% BS1 threshold used here.
Computational splice prediction does not support a damaging effect, as SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, and the variant-level splice assessment indicates that this synonymous change is not in a canonical splice-site position.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at low frequency in population databases. In gnomAD v2.1 the overall AF is 0.00396% and in gnomAD v4.1 the overall AF is 0.00399%; the highest observed subpopulation frequency in gnomAD v4.1 is 0.04636%, which is below the 0.1% threshold used here for PM2. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF 3.95514e-05 (7/176985)
- gnomAD v4.1 AF 3.98855e-05 (48/1203445)
- Highest observed subpopulation AF 0.000463607 in Middle Eastern individuals
Sources
BP7 SupportingThis is a synonymous variant, p.(Asp1488=), and available computational evidence predicts no significant effect on splicing. SpliceAI shows a maximum delta score of 0.01, and the variant-level splice assessment indicates that it is not in a canonical splice consensus position, supporting BP7. Details ▾Hide ▴
Evidence considered
- Synonymous protein consequence p.(Asp1488=)
- SpliceAI max delta score 0.01
- Canonical splice consensus false in variant-level assessment
Still missing
- No RNA study was identified for direct transcript confirmation.
Sources
spliceai ↗pvs1_variant_assessment
Not met · 5 · evaluated, threshold not reached
PVS1 BCORL1 loss of function is an established germline disease mechanism, but this variant is a synonymous change, p.(Asp1488=), and the generic PVS1 assessment found that it is not a nonsense, frameshift, or canonical +/-1,2 splice-site variant. Available evidence does not support applying PVS1. Details ▾Hide ▴
Evidence considered
- BCORL1 loss-of-function mechanism supported at the gene level
- Variant-level PVS1 scaffold did not place this synonymous variant in a generic PVS1-eligible null-variant bucket
Still missing
- No RNA study was identified for this exact variant.
Sources
PM1 This synonymous variant has not been shown to lie in a well-established mutational hotspot or critical functional region without benign variation. Cancer Hotspots did not identify a statistically significant hotspot at this site. Details ▾Hide ▴
Evidence considered
- No hotspot row or significant hotspot evidence identified for residue D1488
Still missing
- No curated pathogenic cluster centered on this exact site was identified.
Sources
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.01, and the variant is not in a canonical splice-site position. REVEL, BayesDel, and HCI prior scores were not available for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01
- Variant-level assessment marked canonical splice consensus as false
- REVEL not found
- BayesDel not found
- HCI prior not available for BCORL1
Still missing
- No RNA study was identified to directly confirm transcript effect.
Sources
spliceai ↗pvs1_variant_assessment
BA1 The population frequency does not meet a stand-alone benign threshold. The highest observed subpopulation frequency in gnomAD v4.1 is 0.04636%, which is below the 1% BA1 threshold used here. Details ▾Hide ▴
Evidence considered
- Highest observed subpopulation AF 0.000463607 in Middle Eastern individuals
Sources
BS1 The population frequency is below the benign strong threshold. The highest observed subpopulation frequency in gnomAD v4.1 is 0.04636%, which is below the 0.3% BS1 threshold used here. Details ▾Hide ▴
Evidence considered
- Highest observed subpopulation AF 0.000463607 in Middle Eastern individuals
Sources
Not assessed · 14 · no assessment recorded
PS2 No confirmed de novo observation with established maternity and paternity was identified for this variant. Details ▾Hide ▴
Evidence considered
- No ClinVar record for the exact variant
Still missing
- No trio-based case report or clinical submission describing this exact variant was identified.
Sources
PS3 No well-established functional study or RNA assay was identified for this exact variant, so PS3 cannot be assessed. Details ▾Hide ▴
Evidence considered
- OncoKB did not provide variant-specific functional evidence
- Only computational splice prediction was available
Still missing
- No variant-specific functional or transcript study was identified.
Sources
PS4 No enrichment data or multiple affected germline observations were identified for this exact variant, so PS4 cannot be applied. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar
Still missing
- No case-control or recurrence data for this exact variant were identified.
Sources
PM6 No assumed de novo observation was identified for this variant, so PM6 cannot be assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar submissions for the exact variant
Still missing
- No partial parent-testing evidence for this exact variant was identified.
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with family data
Still missing
- No family-level segregation report for this exact variant was identified.
Sources
PP4 No phenotype information specific to the tested individual was available to determine whether the clinical presentation is highly specific for a BCORL1-related disorder. Details ▾Hide ▴
Still missing
- Phenotype data for the individual carrying this variant were not provided.
PP5 No reputable source classification for this exact germline variant was identified. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar
Still missing
- No ClinVar or expert-panel classification for this exact variant was identified.
Sources
BS2 Population data show rare alleles in gnomAD, but no evidence was identified demonstrating occurrence in definitively unaffected individuals at a level sufficient for BS2. Details ▾Hide ▴
Evidence considered
- Rare allele counts in gnomAD without phenotype information
Still missing
- No phenotype-confirmed unaffected carrier data were identified.
Sources
BS3 No well-established functional study showing no damaging effect was identified for this variant. Details ▾Hide ▴
Evidence considered
- OncoKB did not provide variant-specific functional evidence
Still missing
- No variant-specific benign functional or RNA assay was identified.
Sources
BS4 No family data were identified showing lack of segregation with disease, so BS4 cannot be assessed. Details ▾Hide ▴
Evidence considered
- No ClinVar record with family information
Still missing
- No discordant family observations for this exact variant were identified.
Sources
BP2 No phase information or co-occurrence data were identified for this variant, so BP2 cannot be assessed. Details ▾Hide ▴
Still missing
- No co-occurrence or phase data were identified.
BP4 Computational data do not suggest splice disruption, with SpliceAI maximum delta score 0.01, but no broader multi-predictor benign framework was available for this synonymous variant beyond splice prediction alone. BP4 was therefore not separately applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01
- REVEL not found
- BayesDel not found
Still missing
- No additional applicable computational predictors beyond splice prediction were available for this synonymous variant.
Sources
BP5 No alternate molecular basis for the phenotype was provided, so BP5 cannot be assessed. Details ▾Hide ▴
Still missing
- No phenotype-level differential or alternate genetic explanation was provided.
BP6 No reputable source reported this exact variant as benign or likely benign. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar
Still missing
- No ClinVar benign or likely benign submission was identified for this exact variant.
Sources
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies when a different nucleotide change produces the same pathogenic amino acid substitution. This variant is synonymous and does not alter the amino acid sequence, so PS1 is not applicable. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Asp1488=)
PM3 N/APM3 is used for recessive disorders with pathogenic variants observed in trans. No such trans configuration evidence is relevant for this single synonymous BCORL1 variant assessment. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to protein length changes from in-frame insertions, deletions, or stop-loss variants. This variant is synonymous and does not change protein length. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Asp1488=)
PM5 N/APM5 applies to novel missense changes at an amino acid residue where a different pathogenic missense change has been established. This variant is synonymous, and PM5 candidate review did not support classic same-residue PM5 use. Details ▾Hide ▴
Evidence considered
- PM5 artifact marked classic same-residue PM5 search as not eligible
Sources
pm5_candidates
PP2 N/APP2 is a missense criterion. This variant is synonymous, so PP2 is not applicable. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Asp1488=)
BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary disease mechanism. This variant is synonymous, so BP1 is not applicable. Details ▾Hide ▴
Evidence considered
- Predicted protein consequence is p.(Asp1488=)
BP3 N/ABP3 applies to in-frame insertions or deletions in repetitive regions without known function. This variant is a synonymous single-nucleotide substitution, so BP3 is not applicable. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BCORL1
- Transcript
- NM_021946.4
- Coding (HGVS c.)
- NM_021946.4:c.4464C>T
- Protein (HGVS p.)
- NP_068765.3:p.(Asp1488=)
- GRCh38
- chrX:130037525 C>T
- GRCh37
- chrX:129171500 C>T
- COSMIC
- COSV54397317
Gene diagram
Every interpreted variant in BCORL1, mapped onto the exon structure of NM_021946.4. Select a row to find it on the plot.
BCORL1NM_021946.4
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 BCORL1
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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
48 / 1,203,445 alleles
AF 3.99e-05 · 0 homozygotes · FAF 0.00011
gnomAD v2.1
7 / 176,985 alleles
AF 3.96e-05 · 0 homozygotes · FAF 4.58e-05
By genetic ancestry
gnomAD v4.1
AF 4e-05 · 48 / 1,203,445 alleles · 0 hom · FAF 0.00011
| Middle Eastern2 / 4,314 | 0.00046 |
| South Asian11 / 55,844 | 0.0002 |
| East Asian2 / 33,565 | 6e-05 |
| Ashkenazi Jewish1 / 21,705 | 4.6e-05 |
| European (non-Finnish)31 / 891,137 | 3.5e-05 |
| Remaining individuals1 / 47,335 | 2.1e-05 |
0 alternate alleles recorded in 4 other groups: Admixed American, European (Finnish), Amish, African/African American.
gnomAD v2.1
AF 4e-05 · 7 / 176,985 alleles · 0 hom · FAF 4.6e-05
| South Asian3 / 17,713 | 0.00017 |
| Ashkenazi Jewish1 / 7,020 | 0.00014 |
| European (non-Finnish)3 / 78,510 | 3.8e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.98855e-05; MAF= 0.00399%, 48/1203445 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000463607; MAF= 0.04636%, 2/4314 alleles, homozygotes = 0); grpmax FAF= 0.00011029.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.95514e-05; MAF= 0.00396%, 7/176985 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000169367; MAF= 0.01694%, 3/17713 alleles, homozygotes = 0); grpmax FAF= 4.577e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP7 SupportingThis is a synonymous variant, p.(Asp1488=), and available computational evidence predicts no significant effect on splicing. SpliceAI shows a maximum delta score of 0.01, and the variant-level splice assessment indicates that it is not in a canonical splice consensus position, supporting BP7. Details ▾Hide ▴
Evidence considered
- Synonymous protein consequence p.(Asp1488=)
- SpliceAI max delta score 0.01
- Canonical splice consensus false in variant-level assessment
Still missing
- No RNA study was identified for direct transcript confirmation.
Sources
spliceai ↗pvs1_variant_assessment
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.01, and the variant is not in a canonical splice-site position. REVEL, BayesDel, and HCI prior scores were not available for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01
- Variant-level assessment marked canonical splice consensus as false
- REVEL not found
- BayesDel not found
- HCI prior not available for BCORL1
Still missing
- No RNA study was identified to directly confirm transcript effect.
Sources
spliceai ↗pvs1_variant_assessment
BP4 Computational data do not suggest splice disruption, with SpliceAI maximum delta score 0.01, but no broader multi-predictor benign framework was available for this synonymous variant beyond splice prediction alone. BP4 was therefore not separately applied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01
- REVEL not found
- BayesDel not found
Still missing
- No additional applicable computational predictors beyond splice prediction were available for this synonymous variant.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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
48 / 1,203,445 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
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/?term=NM_021946.4%3Ac.4464C%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/X-129171500-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chrX-130037525-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_021946.4%3Ac.4464…
- OncoKB ↗www.oncokb.org/gene/BCORL1/D1488=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=162421195
- 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= 3.98855e-05; MAF= 0.00399%, 48/1203445 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000463607; MAF= 0.04636%, 2/4314 alleles, homozygotes = 0); grpmax FAF= 0.00011029.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.95514e-05; MAF= 0.00396%, 7/176985 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000169367; MAF= 0.01694%, 3/17713 alleles, homozygotes = 0); grpmax FAF= 4.577e-05.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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; COSV54397317, n = 5 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.