X-40064533-A-G

Position:

chrX-40064533-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001123385.2(BCOR):c.3305T>C(p.Val1102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,210,388 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 6 hem., cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 7 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.339

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021849632).

BP6

Variant X-40064533-A-G is Benign according to our data. Variant chrX-40064533-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210520.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000258 (29/112362) while in subpopulation AFR AF= 0.000905 (28/30945). AF 95% confidence interval is 0.000643. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.3305T>C	p.Val1102Ala	missense_variant	7/15	ENST00000378444.9	NP_001116857.1	Q6W2J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 link	c.3305T>C	p.Val1102Ala	missense_variant	7/15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.000249

AC:

AN:

112310

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34494

show subpopulations

Gnomad AFR

AF:

0.000874

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

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:

0.0000274

AC:

AN:

182652

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67430

show subpopulations

Gnomad AFR exome

AF:

0.000380

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1098026

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363386

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.000258

AC:

AN:

112362

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34556

show subpopulations

Gnomad4 AFR

AF:

0.000905

Gnomad4 AMR

AF:

0.0000931

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

Bravo

AF:

0.000170

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 12, 2015

- -

BCOR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 15, 2022

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.48

DEOGEN2

Benign

0.10

.;.;.;T;.;T

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.48

T;.;T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.022

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

.;N;.;N;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.18

N;N;N;N;N;N

REVEL

Benign

0.086

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T;.

Polyphen

0.0

.;B;B;B;B;.

Vest4

0.080, 0.10, 0.10, 0.064

MutPred

0.045

.;Gain of loop (P = 0.024);.;Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);

MVP

0.32

MPC

0.32

ClinPred

0.018

GERP RS

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.039

gMVP

0.087

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