X-40074086-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001123385.2(BCOR):c.1260T>C(p.Asp420Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 31517 hom., 30649 hem., cov: 24)

Exomes 𝑓: 0.88 ( 285959 hom. 317776 hem. )

Failed GnomAD Quality Control

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.0430

Publications

29 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-40074086-A-G is Benign according to our data. Variant chrX-40074086-A-G is described in ClinVar as Benign. ClinVar VariationId is 95764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.043 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.1260T>C	p.Asp420Asp	synonymous_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.1260T>C	p.Asp420Asp	synonymous_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes

AF:

0.901

AC:

100569

AN:

111671

Hom.:

31517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.925

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.971

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.946

Gnomad MID

AF:

0.890

Gnomad NFE

AF:

0.880

Gnomad OTH

AF:

0.899

GnomAD2 exomes

AF:

0.897

AC:

163861

AN:

182605

AF XY:

0.885

show subpopulations

Gnomad AFR exome

AF:

0.924

Gnomad AMR exome

AF:

0.955

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

0.973

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.881

Gnomad OTH exome

AF:

0.890

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.879

AC:

965553

AN:

1097944

Hom.:

285959

Cov.:

AF XY:

0.875

AC XY:

317776

AN XY:

363318

show subpopulations

African (AFR)

AF:

0.924

AC:

24398

AN:

26401

American (AMR)

AF:

0.951

AC:

33493

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

17443

AN:

19386

East Asian (EAS)

AF:

0.982

AC:

29664

AN:

30200

South Asian (SAS)

AF:

0.774

AC:

41882

AN:

54126

European-Finnish (FIN)

AF:

0.937

AC:

37881

AN:

40432

Middle Eastern (MID)

AF:

0.861

AC:

3560

AN:

4136

European-Non Finnish (NFE)

AF:

0.875

AC:

736645

AN:

841971

Other (OTH)

AF:

0.881

AC:

40587

AN:

46088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5769

11538

17306

23075

28844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20248

40496

60744

80992

101240

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.901

AC:

100630

AN:

111723

Hom.:

31517

Cov.:

AF XY:

0.905

AC XY:

30649

AN XY:

33883

show subpopulations

African (AFR)

AF:

0.922

AC:

28413

AN:

30810

American (AMR)

AF:

0.925

AC:

9856

AN:

10653

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

2410

AN:

2648

East Asian (EAS)

AF:

0.971

AC:

3405

AN:

3506

South Asian (SAS)

AF:

0.784

AC:

2101

AN:

2680

European-Finnish (FIN)

AF:

0.946

AC:

5641

AN:

5962

Middle Eastern (MID)

AF:

0.893

AC:

192

AN:

215

European-Non Finnish (NFE)

AF:

0.880

AC:

46682

AN:

53051

Other (OTH)

AF:

0.901

AC:

1374

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

377

755

1132

1510

1887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.890

Hom.:

79634

Bravo

AF:

0.902

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

Mar 19, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oculofaciocardiodental syndrome

Benign:3

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Inborn genetic diseases

Benign:1

Jun 22, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.54

(source)

DANN

Benign

0.36

PhyloP100

0.043

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(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