Genetic Variant NM_001123385.2:c.1232G>C (chrX-40074114-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001123385.2(BCOR):c.1232G>C(p.Arg411Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,097,850 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R411W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000013 ( 0 hom. 3 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2405718).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.1232G>C	p.Arg411Pro	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.1232G>C	p.Arg411Pro	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000439

AC:

AN:

182074

AF XY:

0.0000300

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:

0.000507

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1097850

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26397

American (AMR)

AF:

0.00

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.00

AC:

AN:

54076

European-Finnish (FIN)

AF:

0.000247

AC:

AN:

40453

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

841948

Other (OTH)

AF:

0.0000217

AC:

AN:

46078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;T;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D;D;D;D

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

M;M;M;M;.

PhyloP100

2.3

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Benign

0.26

T;D;T;T;.

Polyphen

1.0

D;D;D;D;.

Vest4

0.59

MutPred

0.25

Loss of MoRF binding (P = 0.0317);Loss of MoRF binding (P = 0.0317);Loss of MoRF binding (P = 0.0317);Loss of MoRF binding (P = 0.0317);Loss of MoRF binding (P = 0.0317);

MVP

0.65

MPC

1.1

ClinPred

0.38

GERP RS

5.6

Varity_R

0.47

gMVP

0.31

Mutation Taster

=58/42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over