dbSNP rs145327925: BCOR:p.Val1138Ala (chrX-40064425-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001123385.2(BCOR):c.3413T>C(p.Val1138Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,210,794 control chromosomes in the GnomAD database, including 2 homozygotes. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00078 ( 1 hom., 31 hem., cov: 24)

Exomes 𝑓: 0.000084 ( 1 hom. 23 hem. )

Consequence

BCOR
NM_001123385.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0790

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061370134).

BP6

Variant X-40064425-A-G is Benign according to our data. Variant chrX-40064425-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000782 (88/112567) while in subpopulation AFR AF = 0.00277 (86/31023). AF 95% confidence interval is 0.0023. There are 1 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 31 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123385.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCOR	NM_001123385.2	MANE Select	c.3413T>C	p.Val1138Ala	missense	Exon 7 of 15	NP_001116857.1
BCOR	NM_001437510.1		c.3413T>C	p.Val1138Ala	missense	Exon 7 of 15	NP_001424439.1
BCOR	NM_001438207.1		c.3359T>C	p.Val1120Ala	missense	Exon 6 of 14	NP_001425136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCOR	ENST00000378444.9	TSL:1 MANE Select	c.3413T>C	p.Val1138Ala	missense	Exon 7 of 15	ENSP00000367705.4
BCOR	ENST00000397354.7	TSL:1	c.3413T>C	p.Val1138Ala	missense	Exon 7 of 15	ENSP00000380512.3
BCOR	ENST00000378455.8	TSL:1	c.3359T>C	p.Val1120Ala	missense	Exon 6 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes

AF:

0.000791

AC:

AN:

112515

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000185

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000290

AC:

AN:

183020

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.00350

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000838

AC:

AN:

1098227

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

363581

show subpopulations

African (AFR)

AF:

0.00288

AC:

AN:

26402

American (AMR)

AF:

0.000170

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40519

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842132

Other (OTH)

AF:

0.000174

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000782

AC:

AN:

112567

Hom.:

Cov.:

AF XY:

0.000892

AC XY:

AN XY:

34763

show subpopulations

African (AFR)

AF:

0.00277

AC:

AN:

31023

American (AMR)

AF:

0.000185

AC:

AN:

10797

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3552

South Asian (SAS)

AF:

0.00

AC:

AN:

2734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53170

Other (OTH)

AF:

0.00

AC:

AN:

1542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000621

Hom.:

Bravo

AF:

0.000842

ESP6500AA

AF:

0.00417

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 21, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oculofaciocardiodental syndrome

Benign:1

Sep 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0094

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.64

M_CAP

Benign

0.014

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

PhyloP100

0.079

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.10

REVEL

Benign

0.033

Sift

Benign

0.26

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.099

MVP

0.39

MPC

0.32

ClinPred

0.0090

GERP RS

-0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.076

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over