X-40062275-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP5BP4BS1_SupportingBS2

The NM_001123385.2(BCOR):c.4292C>A(p.Ser1431Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,209,005 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.000054 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.000019 ( 0 hom. 4 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.45

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

PP5

Variant X-40062275-G-T is Pathogenic according to our data. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203. Variant chrX-40062275-G-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 402203.

BP4

Computational evidence support a benign effect (MetaRNN=0.20105365). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000538 (6/111557) while in subpopulation AMR AF = 0.000285 (3/10525). AF 95% confidence interval is 0.0000772. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 2 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.4292C>A	p.Ser1431Tyr	missense_variant	Exon 10 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.4292C>A	p.Ser1431Tyr	missense_variant	Exon 10 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111557

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000445

AC:

AN:

179944

AF XY:

0.0000462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1097448

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

362842

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26395

American (AMR)

AF:

0.000285

AC:

AN:

35148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19375

East Asian (EAS)

AF:

0.00

AC:

AN:

30186

South Asian (SAS)

AF:

0.00

AC:

AN:

53879

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40453

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000950

AC:

AN:

841816

Other (OTH)

AF:

0.0000434

AC:

AN:

46062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000538

AC:

AN:

111557

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33727

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30647

American (AMR)

AF:

0.000285

AC:

AN:

10525

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3552

South Asian (SAS)

AF:

0.00

AC:

AN:

2643

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53065

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Abnormal brain morphology

Pathogenic:1

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

not specified

Uncertain:1

May 04, 2022

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculofaciocardiodental syndrome

Uncertain:1

Mar 26, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

.;T;.;.;T;.;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

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

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.90

.;.;.;.;L;.;.

PhyloP100

5.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.023

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

Polyphen

0.65, 0.66

.;.;P;P;P;P;.

Vest4

0.72, 0.30, 0.34, 0.33, 0.29

MVP

0.65

MPC

0.56

ClinPred

0.37

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.32

Mutation Taster

=95/5

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over