chrX-40073654-T-C

Position:

chrX-40073654-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001123385.2(BCOR):c.1692A>G(p.Ala564Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,210,479 control chromosomes in the GnomAD database, including 26,452 homozygotes. There are 71,066 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8378 hom., 11497 hem., cov: 25)

Exomes 𝑓: 0.16 ( 18074 hom. 59569 hem. )

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -5.09

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:

BCOR (HGNC:):

BCOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-40073654-T-C is Benign according to our data. Variant chrX-40073654-T-C is described in ClinVar as [Benign]. Clinvar id is 95766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40073654-T-C is described in Lovd as [Likely_benign]. Variant chrX-40073654-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.1692A>G	p.Ala564Ala	synonymous_variant	4/15	ENST00000378444.9	NP_001116857.1	Q6W2J9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.1692A>G	p.Ala564Ala	synonymous_variant	4/15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

38174

AN:

112365

Hom.:

8372

Cov.:

AF XY:

0.331

AC XY:

11437

AN XY:

34557

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.253

AC:

46239

AN:

182781

Hom.:

7228

AF XY:

0.243

AC XY:

16370

AN XY:

67309

show subpopulations

Gnomad AFR exome

AF:

0.814

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.707

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.157

AC:

172780

AN:

1098058

Hom.:

18074

Cov.:

AF XY:

0.164

AC XY:

59569

AN XY:

363428

show subpopulations

Gnomad4 AFR exome

AF:

0.820

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.0986

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.340

AC:

38243

AN:

112421

Hom.:

8378

Cov.:

AF XY:

0.332

AC XY:

11497

AN XY:

34623

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.160

Hom.:

10047

Bravo

AF:

0.374

EpiCase

AF:

0.111

EpiControl

AF:

0.109

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 30, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Oculofaciocardiodental syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.012

DANN

Benign

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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