About BCORL1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BCORL1 c.2361A>T, p.(Pro787=)
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 very low frequency in population databases and remains below the default non-VCEP PM2 threshold of 0.1%. In gnomAD v2.1 the allele frequency is 0.00164% (3/183251; grpmax FAF 9.75e-06), and in gnomAD v4.1 the allele frequency is 0.00107% (13/1212241; grpmax FAF 8.1e-06).
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Available computational evidence supports no predicted molecular impact. This variant is synonymous at p.(Pro787=), and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00.
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, BP4 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
13 / 1,212,241 alleles
gnomAD v4.1: 13 / 1,212,241 alleles. Recorded AF 1.07239e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.6371e-05; MAF= 0.00164%, 3/183251 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.66928e-05; MAF= 0.00367%, 3/81760 alleles, homozygotes = 0); grpmax FAF= 9.75e-06.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
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
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 · 4 not met · 14 not assessed · 8 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 c.2361A>T (p.Pro787=) variant has not been reported in ClinVar.
This variant is present in gnomAD at 0.00164% in v2.1 (3/183251 alleles; grpmax FAF 9.75e-06) and 0.00107% in v4.1 (13/1212241 alleles; grpmax FAF 8.1e-06), which is below the default non-VCEP PM2 threshold of 0.1%.
SpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.00, arguing against a computationally predicted splice-disrupting effect.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at very low frequency in population databases and remains below the default non-VCEP PM2 threshold of 0.1%. In gnomAD v2.1 the allele frequency is 0.00164% (3/183251; grpmax FAF 9.75e-06), and in gnomAD v4.1 the allele frequency is 0.00107% (13/1212241; grpmax FAF 8.1e-06). Details ▾Hide ▴
Rule
generic_acmg_pm2_default_threshold
Evidence considered
- gnomAD v2.1 AF 1.6371e-05
- gnomAD v4.1 AF 1.07239e-05
Sources
BP4 SupportingAvailable computational evidence supports no predicted molecular impact. This variant is synonymous at p.(Pro787=), and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Synonymous protein consequence
- SpliceAI max delta score 0.00
Still missing
- No additional benign computational predictors were available in the reviewed sources.
Sources
Not met · 4 · evaluated, threshold not reached
PM1 This variant does not lie in a statistically significant hotspot, and no evidence was identified that codon 787 is in a well-established critical functional region without benign variation. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Cancer Hotspots review found no hotspot row for BCORL1 P787
- OncoKB context was not variant-specific
Still missing
- No domain-specific pathogenic clustering evidence for this residue was identified.
Sources
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- SpliceAI max delta score 0.00
Still missing
- No additional damaging computational predictors were identified in the reviewed sources.
Sources
BA1 Population frequency does not reach the BA1 threshold of 1%. The highest reviewed population frequency is 0.00164% in gnomAD v2.1 and 0.00107% in gnomAD v4.1, both well below 1%. Details ▾Hide ▴
Rule
generic_acmg_ba1_default_threshold
Evidence considered
- gnomAD v2.1 AF 1.6371e-05
- gnomAD v4.1 AF 1.07239e-05
Sources
BS1 Population frequency does not exceed the default non-VCEP BS1 threshold of 0.3%. The highest reviewed population frequency is 0.00164% in gnomAD v2.1 and 0.00107% in gnomAD v4.1, both below 0.3%. Details ▾Hide ▴
Rule
generic_acmg_bs1_default_threshold
Evidence considered
- gnomAD v2.1 AF 1.6371e-05
- gnomAD v4.1 AF 1.07239e-05
Sources
Not assessed · 14 · no assessment recorded
PS2 No confirmed de novo occurrence with verified maternity and paternity was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No case-level parental testing data were identified.
Sources
PS3 No well-established functional or RNA study demonstrating a damaging effect of this exact variant was identified. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- OncoKB did not provide variant-specific functional evidence
- SpliceAI is predictive only and does not replace functional testing
Still missing
- No minigene
- RT-PCR
- or other functional assay for this exact variant was identified.
Sources
PS4 No enrichment data in affected individuals versus controls were identified for this variant. The available sources do not provide case counts sufficient to support increased prevalence in affected individuals. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No case-control data were identified.
- No affected proband series for this exact variant were identified.
Sources
PM6 No presumed de novo report was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No case report with partial parental testing was identified.
Sources
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No pedigree or family co-segregation data were identified.
Sources
PP4 No phenotype-specific clinical evidence was provided to show that the observed presentation is highly specific for BCORL1-related disease. Details ▾Hide ▴
Rule
generic_acmg
Still missing
- Detailed phenotype correlation data were not available for review.
PP5 No reputable external source classification for this exact variant was identified that could support PP5. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No submitted pathogenic classification for this exact variant was identified.
Sources
BS2 The reviewed data do not establish observation of this variant in a number of healthy individuals sufficient for BS2. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Low-count population observations without BS2-specific healthy-carrier context
Still missing
- No healthy-carrier dataset interpretation specific to BS2 was identified.
Sources
BS3 No well-established functional or RNA study showing a normal effect for this exact variant was identified. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- SpliceAI is computational only
- OncoKB did not provide variant-specific benign functional evidence
Still missing
- No negative RNA or functional assay for this exact variant was identified.
Sources
BS4 No family study showing lack of segregation with disease was identified for this variant. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No non-segregation data were identified.
Sources
BP2 No phase data were identified to determine whether this variant occurs in trans with a pathogenic variant or in cis with another variant. Details ▾Hide ▴
Rule
generic_acmg
Still missing
- No phasing information was identified.
BP5 No alternate molecular explanation for disease was identified in the reviewed materials, so BP5 was not assessed. Details ▾Hide ▴
Rule
generic_acmg
Still missing
- No comprehensive alternate-cause evaluation was available.
BP6 No reputable benign external classification was identified for this exact variant. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- ClinVar has no entry for this variant
Still missing
- No submitted benign classification for this exact variant was identified.
Sources
BP7 This is a synonymous variant and SpliceAI predicts no significant splice impact, but the reviewed sources did not provide nucleotide conservation evidence needed for a complete BP7 assessment. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Synonymous protein consequence
- SpliceAI max delta score 0.00
Still missing
- No nucleotide conservation assessment was identified.
Sources
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is synonymous at p.(Pro787=) and does not fall into the generic PVS1 null-variant categories of nonsense, frameshift, or canonical +/-1,2 splice-site variants. Although loss of function is an established disease mechanism for BCORL1, the available evidence does not support applying PVS1 to this specific change. Details ▾Hide ▴
Rule
generic_acmg_pvs1_fallback
Evidence considered
- BCORL1 loss-of-function mechanism supported at the gene level
- Variant-level generic PVS1 scaffold does not place this synonymous change in a PVS1 bucket
Still missing
- No RNA study for this exact variant was identified.
Sources
PS1 N/AThis criterion is intended for variants that produce the same amino acid change as an established pathogenic variant. This variant is synonymous and no amino acid substitution is present. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Protein consequence is p.(Pro787=)
PM3 N/AThis criterion is used for recessive disorders with pathogenic variants observed in trans. The reviewed evidence does not support applying PM3 to this BCORL1 variant. Details ▾Hide ▴
Rule
generic_acmg
PM4 N/AThis variant does not change protein length and is not an in-frame insertion or deletion. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Protein consequence is synonymous
PM5 N/APM5 applies to novel missense changes at a residue where another pathogenic missense change is established. This variant is synonymous, and the reviewed PM5 candidate collection did not support classic same-residue PM5 use. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- PM5 candidate file marked classic same-residue PM5 as not safely applicable
Sources
pm5_candidates
PP2 N/APP2 is a missense-based criterion and is not applicable to this synonymous variant. Details ▾Hide ▴
Rule
generic_acmg
BP1 N/ABP1 is a missense-based criterion and is not applicable to this synonymous variant. Details ▾Hide ▴
Rule
generic_acmg
BP3 N/AThis criterion applies to in-frame insertions or deletions in repetitive regions and is not applicable to this synonymous single-nucleotide variant. Details ▾Hide ▴
Rule
generic_acmg
Identifiers
- Gene
- BCORL1
- Transcript
- NM_021946.4
- Coding (HGVS c.)
- NM_021946.4:c.2361A>T
- Protein (HGVS p.)
- NP_068765.3:p.(Pro787=)
- GRCh38
- chrX:130015133 A>T
- GRCh37
- chrX:129149109 A>T
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
13 / 1,212,241 alleles
AF 1.07e-05 · 0 homozygotes · FAF 8.1e-06
gnomAD v2.1
3 / 183,251 alleles
AF 1.64e-05 · 0 homozygotes · FAF 9.75e-06
By genetic ancestry
gnomAD v4.1
AF 1.1e-05 · 13 / 1,212,241 alleles · 0 hom · FAF 8.1e-06
| European (non-Finnish)13 / 895,613 | 1.5e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.6e-05 · 3 / 183,251 alleles · 0 hom · FAF 9.7e-06
| European (non-Finnish)3 / 81,760 | 3.7e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.07239e-05; MAF= 0.00107%, 13/1212241 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.45152e-05; MAF= 0.00145%, 13/895613 alleles, homozygotes = 0); grpmax FAF= 8.1e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.6371e-05; MAF= 0.00164%, 3/183251 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.66928e-05; MAF= 0.00367%, 3/81760 alleles, homozygotes = 0); grpmax FAF= 9.75e-06.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingAvailable computational evidence supports no predicted molecular impact. This variant is synonymous at p.(Pro787=), and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Synonymous protein consequence
- SpliceAI max delta score 0.00
Still missing
- No additional benign computational predictors were available in the reviewed sources.
Sources
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- SpliceAI max delta score 0.00
Still missing
- No additional damaging computational predictors were identified in the reviewed sources.
Sources
BP7 This is a synonymous variant and SpliceAI predicts no significant splice impact, but the reviewed sources did not provide nucleotide conservation evidence needed for a complete BP7 assessment. Details ▾Hide ▴
Rule
generic_acmg
Evidence considered
- Synonymous protein consequence
- SpliceAI max delta score 0.00
Still missing
- No nucleotide conservation assessment was identified.
Sources
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
13 / 1,212,241 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
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_021946.4%3Ac.2361A%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/X-129149109-A-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chrX-130015133-A-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_021946.4%3Ac.2361…
- OncoKB ↗www.oncokb.org/gene/BCORL1/P787=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BCORL1+c.2361A%3ET
- 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= 1.07239e-05; MAF= 0.00107%, 13/1212241 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.45152e-05; MAF= 0.00145%, 13/895613 alleles, homozygotes = 0); grpmax FAF= 8.1e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.6371e-05; MAF= 0.00164%, 3/183251 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.66928e-05; MAF= 0.00367%, 3/81760 alleles, homozygotes = 0); grpmax FAF= 9.75e-06.
ClinVar
This variant is absent from ClinVar.
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.