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BCORL1
Final classification
VUS
BCORL1 c.2361A>T · p.Pro787=
BCORL1

The BCORL1 c.2361A>T (p.Pro787=) variant has not been reported in ClinVar.

Gene
BCORL1
Transcript
NM_021946.4
HGVS · transcript:coding
NM_021946.4:c.2361A>T
Consequence
N/A
GRCh38
chrX:130015133 A>T
GRCh37
chrX:129149109 A>T
Basis 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. ▾
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.
Classification rationale
PM2 BP4 VUS
BCORL1 c.2361A>T

The BCORL1 c.2361A>T (p.Pro787=) variant has not been reported in ClinVar.1 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%.2 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.3

PM2 + BP4 → VUS
1 clinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗
3 spliceai ↗
Gene diagram · NM_021946.4 · variants mapped to exon structure
BCORL1 NM_021946.4
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      —
      Research & evidence
      Population frequency
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      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.
      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.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      0.0011% · 13 / 1,212,241
      0 hom · FAF 0.00081%
      European (non-Finnish)
      13 / 895,613
      0.0015%
      + 9 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American)
      gnomAD v2.1
      0.0016% · 3 / 183,251
      0 hom · FAF 0.00097%
      European (non-Finnish)
      3 / 81,760
      0.0037%
      + 7 not observed (African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)
      gnomAD v4 ↗ gnomAD v2 ↗
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
      SpliceAI ↗
      Functional / OncoKB screenshot
      Functional Unknown Oncogenic Effect
      OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant hotspot.
      COSMIC ↗ Hotspots ↗
      Sources & reference links
      7Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots