dbSNP rs17145652: BCOR:p.Ser593Ser (chrX-40073567-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001123385.2(BCOR):c.1779C>T(p.Ser593Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,211,038 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. S593S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.00012 ( 0 hom. 39 hem. )

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.70

Publications

3 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen, Ambry Genetics
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-40073567-G-A is Benign according to our data. Variant chrX-40073567-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3047369.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000619 (7/113068) while in subpopulation NFE AF = 0.0000937 (5/53376). AF 95% confidence interval is 0.0000368. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

BS2

High Hemizygotes in GnomAdExome4 at 39 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	UniProt
BCOR	NM_001123385.2	MANE Select	c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
BCOR	NM_001437510.1		c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 15	NP_001424439.1
BCOR	NM_001438207.1		c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 14	NP_001425136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCOR	ENST00000378444.9	TSL:1 MANE Select	c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
BCOR	ENST00000397354.7	TSL:1	c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
BCOR	ENST00000378455.8	TSL:1	c.1779C>T	p.Ser593Ser	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes

AF:

0.0000619

AC:

AN:

113068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000643

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:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

182959

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000152

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:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

129

AN:

1097970

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363362

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26403

American (AMR)

AF:

0.00

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:

40254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000151

AC:

127

AN:

842134

Other (OTH)

AF:

0.0000217

AC:

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000619

AC:

AN:

113068

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35202

show subpopulations

African (AFR)

AF:

0.0000643

AC:

AN:

31124

American (AMR)

AF:

0.00

AC:

AN:

10808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2785

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000937

AC:

AN:

53376

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BCOR-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.27

(source)

DANN

Benign

0.58

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over