rs587778097

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001123385.2(BCOR):c.1465C>T(p.Pro489Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,098,113 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 5.28

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.35260475).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.1465C>T	p.Pro489Ser	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.1465C>T	p.Pro489Ser	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1098113

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363471

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54137

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40479

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

842073

Other (OTH)

AF:

0.00

AC:

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1465C>T (p.P489S) alteration is located in exon 4 (coding exon 3) of the BCOR gene. This alteration results from a C to T substitution at nucleotide position 1465, causing the proline (P) at amino acid position 489 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;.;T;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;D;D;D;D

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;L;.

PhyloP100

5.3

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.045

D;D;D;D;T

Sift4G

Benign

0.66

T;T;T;T;.

Polyphen

1.0

D;D;D;D;.

Vest4

0.39

MutPred

0.31

Loss of catalytic residue at P489 (P = 0.0028);Loss of catalytic residue at P489 (P = 0.0028);Loss of catalytic residue at P489 (P = 0.0028);Loss of catalytic residue at P489 (P = 0.0028);Loss of catalytic residue at P489 (P = 0.0028);

MVP

0.45

MPC

0.94

ClinPred

0.84

GERP RS

5.8

Varity_R

0.18

gMVP

0.47

Mutation Taster

=62/38

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

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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