rs774040250

Positions:

chrX-40074472-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000378444.9(BCOR):c.874G>T(p.Gly292Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,204,010 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000012 ( 0 hom. 9 hem. )

Consequence

BCOR
ENST00000378444.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.39

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]

BCOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38435507).

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.874G>T	p.Gly292Cys	missense_variant	4/15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.874G>T	p.Gly292Cys	missense_variant	4/15	1	NM_001123385.2	ENSP00000367705	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34919

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000359

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000306

AC:

AN:

163563

Hom.:

AF XY:

0.0000950

AC XY:

AN XY:

52651

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000292

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1091255

Hom.:

Cov.:

AF XY:

0.0000252

AC XY:

AN XY:

357735

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000226

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000887

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34919

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000359

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 05, 2014

- -

Oculofaciocardiodental syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 12, 2023

This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 292 of the BCOR protein (p.Gly292Cys). This variant is present in population databases (rs774040250, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BCOR-related conditions. ClinVar contains an entry for this variant (Variation ID: 210525). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

.;.;D;.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

.;D;D;D;D

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D;.

Polyphen

1.0

D;D;D;D;.

Vest4

0.66

MutPred

0.29

Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);

MVP

0.82

MPC

0.95

ClinPred

0.57

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.59

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over