X-40054309-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001123385.2(BCOR):c.4766G>A(p.Arg1589His) variant causes a missense change. The variant allele was found at a frequency of 0.0000399 in 1,203,513 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 0.000054 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. 11 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 4.71

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25933474).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000054 (6/111123) while in subpopulation AFR AF= 0.000164 (5/30508). AF 95% confidence interval is 0.0000641. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.4766G>A	p.Arg1589His	missense_variant	Exon 13 of 15	ENST00000378444.9	NP_001116857.1	Q6W2J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 link	c.4766G>A	p.Arg1589His	missense_variant	Exon 13 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111123

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33383

show subpopulations

Gnomad AFR

AF:

0.000164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000960

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000447

AC:

AN:

179058

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63900

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000384

AC:

AN:

1092390

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

358000

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000934

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000358

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111123

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33383

show subpopulations

Gnomad4 AFR

AF:

0.000164

Gnomad4 AMR

AF:

0.0000960

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculofaciocardiodental syndrome

Uncertain:1

Aug 24, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces arginine with histidine at codon 1555 of the BCOR protein (p.Arg1555His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs367859441, ExAC 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: 133690). 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: "Benign"; Align-GVGD: "Class C25"). 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. -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;.;.;D;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;.;D;D;D;D

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.26

T;T;T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.4

.;.;.;.;M;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.4

D;D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.025

D;D;D;D;D;D;T

Sift4G

Uncertain

0.054

T;D;T;T;T;T;D

Polyphen

1.0

.;.;D;D;D;D;.

Vest4

0.097, 0.32, 0.30, 0.34, 0.30

MVP

0.81

MPC

0.33

ClinPred

0.30

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.29

gMVP

0.67

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