Variant rs1041380012 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001123385.2(BCOR):c.2166G>C(p.Leu722Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,098,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000038 ( 0 hom. 9 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22464123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.2166G>C	p.Leu722Phe	missense_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.2166G>C	p.Leu722Phe	missense_variant	4/15	1	NM_001123385.2	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183382

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67828

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1098188

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363550

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:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000475

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculofaciocardiodental syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2021

This sequence change replaces leucine with phenylalanine at codon 722 of the BCOR protein (p.Leu722Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BCOR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

1.0

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0081

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L;L;.;.

MutationTaster

Benign

0.85

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.93

N;N;N;N;N;.

REVEL

Benign

0.087

Sift

Benign

0.079

T;T;T;T;T;.

Sift4G

Uncertain

0.039

D;D;D;D;.;D

Polyphen

0.97

D;D;D;D;.;.

Vest4

0.29

MutPred

0.18

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;

MVP

0.45

MPC

0.97

ClinPred

0.66

GERP RS

4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.18

gMVP

0.51

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