rs749999323

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2

The NM_001123385.2(BCOR):c.1391C>T(p.Thr464Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000512 in 1,210,999 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 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 0.000035 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.000053 ( 0 hom. 21 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.50

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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26442623).

BP6

Variant X-40073955-G-A is Benign according to our data. Variant chrX-40073955-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 576295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000528 (58/1098222) while in subpopulation SAS AF = 0.0000739 (4/54145). AF 95% confidence interval is 0.0000491. There are 0 homozygotes in GnomAdExome4. There are 21 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Hemizygotes in GnomAdExome4 at 21 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.1391C>T	p.Thr464Met	missense_variant	Exon 4 of 15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 link	c.1391C>T	p.Thr464Met	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112777

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000327

AC:

AN:

183443

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1098222

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363576

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26402

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000739

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000629

AC:

AN:

842132

Other (OTH)

AF:

0.0000217

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000355

AC:

AN:

112777

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34915

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31054

American (AMR)

AF:

0.00

AC:

AN:

10747

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3595

South Asian (SAS)

AF:

0.00

AC:

AN:

2772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000750

AC:

AN:

53302

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Oculofaciocardiodental syndrome

Benign:2

Sep 01, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 11, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;T;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

.;T;T;T;T

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;M;M;.

PhyloP100

5.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.0

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.066

T;T;T;T;T

Sift4G

Uncertain

0.043

D;D;D;D;.

Polyphen

1.0

D;D;D;D;.

Vest4

0.43

MutPred

0.22

Loss of glycosylation at T464 (P = 0.0114);Loss of glycosylation at T464 (P = 0.0114);Loss of glycosylation at T464 (P = 0.0114);Loss of glycosylation at T464 (P = 0.0114);Loss of glycosylation at T464 (P = 0.0114);

MVP

0.58

MPC

0.95

ClinPred

0.28

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.11

gMVP

0.35

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over