rs2146825290

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001123385.2(BCOR):​c.5189C>T​(p.Thr1730Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,097,088 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T1730T) has been classified as Benign.

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

1
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73
Variant links:
Genes affected
BCOR (HGNC:20893): (BCL6 corepressor) The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription repressor that is required for germinal center formation and may influence apoptosis. This protein selectively interacts with the POZ domain of BCL6, but not with eight other POZ proteins. Specific class I and II histone deacetylases (HDACs) have been shown to interact with this protein, which suggests a possible link between the two classes of HDACs. Several transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome Y.[provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 2 XLD,XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCORNM_001123385.2 linkc.5189C>T p.Thr1730Met missense_variant Exon 15 of 15 ENST00000378444.9 NP_001116857.1 Q6W2J9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCORENST00000378444.9 linkc.5189C>T p.Thr1730Met missense_variant Exon 15 of 15 1 NM_001123385.2 ENSP00000367705.4 Q6W2J9-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000273
AC:
3
AN:
1097088
Hom.:
0
Cov.:
30
AF XY:
0.00000552
AC XY:
2
AN XY:
362490
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26391
American (AMR)
AF:
0.00
AC:
0
AN:
35120
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19367
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30196
South Asian (SAS)
AF:
0.0000186
AC:
1
AN:
53871
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40485
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4135
European-Non Finnish (NFE)
AF:
0.00000238
AC:
2
AN:
841468
Other (OTH)
AF:
0.00
AC:
0
AN:
46055
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Mar 27, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.5189C>T (p.T1730M) alteration is located in exon 15 (coding exon 14) of the BCOR gene. This alteration results from a C to T substitution at nucleotide position 5189, causing the threonine (T) at amino acid position 1730 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.;.;D;.
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;.;D;D;D
M_CAP
Pathogenic
0.57
D
MetaRNN
Uncertain
0.55
D;D;D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.3
.;.;.;M;.
PhyloP100
5.7
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.4
D;D;D;D;D
REVEL
Benign
0.28
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.021
D;D;D;D;D
Polyphen
1.0
.;D;D;D;D
Vest4
0.61
MutPred
0.41
.;.;.;Loss of helix (P = 0.1299);.;
MVP
0.65
MPC
0.95
ClinPred
0.97
D
GERP RS
5.6
Varity_R
0.34
gMVP
0.53
Mutation Taster
=62/38
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2146825290; hg19: chrX-39911441; API