rs144722432
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001123385.2(BCOR):c.2035G>A(p.Val679Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,208,652 control chromosomes in the GnomAD database, including 1 homozygotes. There are 312 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., 20 hem., cov: 24)
Exomes 𝑓: 0.00086 ( 1 hom. 292 hem. )
Consequence
BCOR
NM_001123385.2 missense
NM_001123385.2 missense
Scores
2
3
10
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.049465537).
BS2
?
High Hemizygotes in GnomAd4 at 20 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCOR | NM_001123385.2 | c.2035G>A | p.Val679Ile | missense_variant | 4/15 | ENST00000378444.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCOR | ENST00000378444.9 | c.2035G>A | p.Val679Ile | missense_variant | 4/15 | 1 | NM_001123385.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000540 AC: 61AN: 113058Hom.: 0 Cov.: 24 AF XY: 0.000568 AC XY: 20AN XY: 35196
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000668 AC: 116AN: 173667Hom.: 0 AF XY: 0.000550 AC XY: 33AN XY: 59961
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GnomAD4 exome AF: 0.000859 AC: 941AN: 1095541Hom.: 1 Cov.: 30 AF XY: 0.000809 AC XY: 292AN XY: 361159
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GnomAD4 genome ? AF: 0.000539 AC: 61AN: 113111Hom.: 0 Cov.: 24 AF XY: 0.000567 AC XY: 20AN XY: 35259
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 08, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 18, 2015 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Microphthalmia, syndromic 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 03, 2017 | - - |
BCOR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 22, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Oculofaciocardiodental syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D;.
Sift4G
Benign
T;T;T;T;.;D
Polyphen
P;P;D;P;.;.
Vest4
MVP
MPC
0.83
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at