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LYFE SCIENCES
Project: HERA
NM_021946.4:c.1111A>C
p.Thr371Pro  ·  BCORL1
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Classification rationale
1

The BCORL1 NM_021946.4:c.1111A>C (NP_068765.3:p.(Thr371Pro)) variant has not been reported in ClinVar.

clinvar ↗
2

This variant is present in gnomAD v2.1 and gnomAD v4.1; in gnomAD v4.1 the highest observed population frequency is 0.21512% in African/African American samples, which is above the default 0.1% PM2 rarity threshold but below the 0.3% BS1 threshold.

gnomad_v2 ↗ gnomad_v4 ↗
3

Cancer Hotspots did not identify a statistically significant hotspot at Thr371, so available evidence does not support PM1.

hotspots ↗
4

Computational evidence does not support a damaging effect: SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and BayesDel is -0.610016, supporting BP4 and arguing against PP3.

spliceai ↗
5

Although BCORL1 loss of function appears to be a relevant disease mechanism, this variant is a missense substitution rather than a qualifying null variant, so the generic PVS1 framework does not apply.

pvs1_generic_framework ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 8.32737e-05; MAF= 0.00833%, 10/120086 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000388387; MAF= 0.03884%, 4/10299 alleles, homozygotes = 0); grpmax FAF= 0.00043111.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000247116; MAF= 0.02471%, 254/1027856 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.00215117; MAF= 0.21512%, 80/37189 alleles, homozygotes = 0); grpmax FAF= 0.00177053.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BCORL1, a transcriptional repressor, is recurrently mutated in hematopoietic malignancies, astrocytomas, and intracranial germ cell tumors.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = -0.610016.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54404421, n = 4 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueT371
Hotspots ↗