Classification rationale

BP7 VUS

BCOR c.4677C>T

The BCOR c.4677C>T (p.Asp1559=) variant has been reported in ClinVar with benign and likely benign classifications from two single submitters.¹ This variant is present in gnomAD v2.1 and v4.1 at low frequency (0.00444%-0.00448%), which is below the default BS1 threshold of 0.3% and BA1 threshold of 1.0%, so population frequency alone does not establish a stand-alone or strong benign criterion.² SpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.00, supporting a benign splicing interpretation consistent with BP7.³ Cancer Hotspots did not identify a statistically significant hotspot at BCOR codon 1559, which does not support PM1.⁴

BP7 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

4 hotspots ↗

Gene diagram · NM_017745.5 · variants mapped to exon structure

BCOR NM_017745.5

Fetching transcript structure from UCSC…

Applied criteria · 1 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= 4.47563e-05; MAF= 0.00448%, 54/1206535 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.78272e-05; MAF= 0.00878%, 4/45544 alleles, homozygotes = 0); grpmax FAF= 3.948e-05.

v2.1

This variant is present in gnomAD v2.1 (AF= 4.43843e-05; MAF= 0.00444%, 8/180244 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.46649e-05; MAF= 0.00747%, 6/80359 alleles, homozygotes = 0); grpmax FAF= 3.178e-05.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.0045% · 54 / 1,206,535
0 hom · FAF 0.0039%

Admixed American 4 / 45,544	0.0088%
European (non-Finnish) 46 / 892,975	0.0052%
Remaining individuals 2 / 47,508	0.0042%
African/African American 2 / 56,928	0.0035%

+ 6 not observed (European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)

gnomAD v2.1

0.0044% · 8 / 180,244
0 hom · FAF 0.0032%

European (non-Finnish) 6 / 80,359	0.0075%
Admixed American 2 / 27,190	0.0074%

+ 6 not observed (African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant has been reported in ClinVar as Benign (1 clinical laboratory) and as Likely benign (1 clinical laboratory).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

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 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