chrX-40072713-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001123385.2(BCOR):c.2633T>C(p.Val878Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,210,391 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 20 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.59

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

microphthalmia, syndromic 2
Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
microphthalmia, Lenz type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

BCOR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044661373).

BP6

Variant X-40072713-A-G is Benign according to our data. Variant chrX-40072713-A-G is described in ClinVar as Benign. ClinVar VariationId is 533721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000051 (56/1098204) while in subpopulation EAS AF = 0.00179 (54/30206). AF 95% confidence interval is 0.00141. There are 0 homozygotes in GnomAdExome4. There are 20 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Hemizygotes in GnomAdExome4 at 20 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.2633T>C	p.Val878Ala	missense_variant	Exon 4 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.2633T>C	p.Val878Ala	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112131

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

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

GnomAD2 exomes

AF:

0.0000817

AC:

AN:

183492

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1098204

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

363560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26401

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00179

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842108

Other (OTH)

AF:

0.0000434

AC:

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112187

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34349

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30898

American (AMR)

AF:

0.00

AC:

AN:

10651

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.000280

AC:

AN:

3575

South Asian (SAS)

AF:

0.00

AC:

AN:

2694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53186

Other (OTH)

AF:

0.00

AC:

AN:

1525

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculofaciocardiodental syndrome

Benign:1

Apr 27, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.11

.;.;T;.;T;.

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.79

.;T;T;T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.045

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N;N;.;.

PhyloP100

3.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.11

N;N;N;N;N;.

REVEL

Benign

0.084

Sift

Uncertain

0.0030

D;D;D;D;D;.

Sift4G

Benign

0.54

T;T;T;T;.;D

Polyphen

0.0010

B;B;B;B;.;.

Vest4

0.11

MutPred

0.26

Gain of ubiquitination at K880 (P = 0.0577);Gain of ubiquitination at K880 (P = 0.0577);Gain of ubiquitination at K880 (P = 0.0577);Gain of ubiquitination at K880 (P = 0.0577);Gain of ubiquitination at K880 (P = 0.0577);.;

MVP

0.65

MPC

0.32

ClinPred

0.091

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over