rs17145653

Positions:

chrX-40073696-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000378444.9(BCOR):c.1650C>T(p.Thr550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,211,722 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,393 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 5 hom., 263 hem., cov: 25)

Exomes 𝑓: 0.0089 ( 32 hom. 3130 hem. )

Consequence

BCOR
ENST00000378444.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.28

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant X-40073696-G-A is Benign according to our data. Variant chrX-40073696-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 95765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40073696-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00787 (894/113567) while in subpopulation NFE AF= 0.0117 (623/53427). AF 95% confidence interval is 0.0109. There are 5 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.1650C>T	p.Thr550=	synonymous_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.1650C>T	p.Thr550=	synonymous_variant	4/15	1	NM_001123385.2	ENSP00000367705	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.00788

AC:

894

AN:

113514

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

263

AN XY:

35648

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.00597

Gnomad ASJ

AF:

0.000376

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000353

Gnomad FIN

AF:

0.000474

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00777

GnomAD3 exomes

AF:

0.00551

AC:

1010

AN:

183300

Hom.:

AF XY:

0.00540

AC XY:

366

AN XY:

67750

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.000801

Gnomad EAS exome

AF:

0.000216

Gnomad SAS exome

AF:

0.000367

Gnomad FIN exome

AF:

0.000816

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00574

GnomAD4 exome

AF:

0.00886

AC:

9731

AN:

1098155

Hom.:

Cov.:

AF XY:

0.00861

AC XY:

3130

AN XY:

363515

show subpopulations

Gnomad4 AFR exome

AF:

0.00280

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.000722

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.000332

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00818

GnomAD4 genome

AF:

0.00787

AC:

894

AN:

113567

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

263

AN XY:

35711

show subpopulations

Gnomad4 AFR

AF:

0.00316

Gnomad4 AMR

AF:

0.00596

Gnomad4 ASJ

AF:

0.000376

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000354

Gnomad4 FIN

AF:

0.000474

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00767

Alfa

AF:

0.00701

Hom.:

Bravo

AF:

0.00782

EpiCase

AF:

0.0123

EpiControl

AF:

0.00883

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 28, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 30, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2016

This alteration is classified as likely 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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Oculofaciocardiodental syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0030

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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