Classification rationale

PM2 BP7 VUS

BCORL1 c.4464C>T

The BCORL1 NM_021946.4:c.4464C>T (p.Asp1488=) variant has not been reported in ClinVar.¹ 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.² 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.³

PM2 + BP7 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗pvs1_variant_assessment

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

gnomAD v2.1

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.

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.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.004% · 48 / 1,203,445
0 hom · FAF 0.011%

Middle Eastern 2 / 4,314	0.046%
South Asian 11 / 55,844	0.02%
East Asian 2 / 33,565	0.006%
Ashkenazi Jewish 1 / 21,705	0.0046%
European (non-Finnish) 31 / 891,137	0.0035%
Remaining individuals 1 / 47,335	0.0021%

+ 4 not observed (Admixed American, European (Finnish), Amish, African/African American)

gnomAD v2.1

0.004% · 7 / 176,985
0 hom · FAF 0.0046%

South Asian 3 / 17,713	0.017%
Ashkenazi Jewish 1 / 7,020	0.014%
European (non-Finnish) 3 / 78,510	0.0038%

+ 5 not observed (African/African American, Admixed American, East Asian, European (Finnish), Remaining individuals)

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV54397317, n = 5 times).

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