X-40052315-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001123385.2(BCOR):c.5062G>C(p.Glu1688Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,210,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
BCOR
NM_001123385.2 missense
NM_001123385.2 missense
Scores
5
10
2
Clinical Significance
Conservation
PhyloP100: 7.42
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: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.845
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000178 AC: 2AN: 112543Hom.: 0 Cov.: 23 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
112543
Hom.:
Cov.:
23
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097975Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1AN XY: 363331 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1097975
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
363331
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26397
American (AMR)
AF:
AC:
1
AN:
35205
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19382
East Asian (EAS)
AF:
AC:
0
AN:
30204
South Asian (SAS)
AF:
AC:
0
AN:
54134
European-Finnish (FIN)
AF:
AC:
0
AN:
40534
Middle Eastern (MID)
AF:
AC:
0
AN:
4135
European-Non Finnish (NFE)
AF:
AC:
0
AN:
841897
Other (OTH)
AF:
AC:
0
AN:
46087
GnomAD4 genome 0.0000178 AC: 2AN: 112543Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34681 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
112543
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
34681
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30947
American (AMR)
AF:
AC:
2
AN:
10636
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2658
East Asian (EAS)
AF:
AC:
0
AN:
3615
South Asian (SAS)
AF:
AC:
0
AN:
2747
European-Finnish (FIN)
AF:
AC:
0
AN:
6138
Middle Eastern (MID)
AF:
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53374
Other (OTH)
AF:
AC:
0
AN:
1505
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Aug 28, 2023
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;T;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;.;.;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;D;D;D;D
Vest4
0.82, 0.64, 0.55, 0.54, 0.76
MutPred
0.68
.;.;.;.;Gain of MoRF binding (P = 0.0683);.;
MVP
MPC
0.92
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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