Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The ENST00000378444.9(BCOR):c.4320T>C(p.Pro1440Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,208,948 control chromosomes in the GnomAD database, including 1 homozygotes. There are 151 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 5 hem., cov: 21)

Exomes 𝑓: 0.00037 ( 1 hom. 146 hem. )

Consequence

BCOR
ENST00000378444.9 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.0520

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.087).

BP6

Variant X-40062247-A-G is Benign according to our data. Variant chrX-40062247-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210522.

BP7

Synonymous conserved (PhyloP=-0.052 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000135 (15/111200) while in subpopulation SAS AF = 0.000766 (2/2611). AF 95% confidence interval is 0.000144. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 5 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378444.9. 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.4320T>C	p.Pro1440Pro	synonymous	Exon 10 of 15	NP_001116857.1
BCOR	NM_001437510.1		c.4320T>C	p.Pro1440Pro	synonymous	Exon 10 of 15	NP_001424439.1
BCOR	NM_001438207.1		c.4266T>C	p.Pro1422Pro	synonymous	Exon 9 of 14	NP_001425136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCOR	ENST00000378444.9	TSL:1 MANE Select	c.4320T>C	p.Pro1440Pro	synonymous	Exon 10 of 15	ENSP00000367705.4
BCOR	ENST00000397354.7	TSL:1	c.4218T>C	p.Pro1406Pro	synonymous	Exon 10 of 15	ENSP00000380512.3
BCOR	ENST00000378455.8	TSL:1	c.4164T>C	p.Pro1388Pro	synonymous	Exon 9 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

111145

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:

0.000764

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000246

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000205

AC:

AN:

180532

AF XY:

0.000229

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:

0.000298

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000367

AC:

403

AN:

1097748

Hom.:

Cov.:

AF XY:

0.000402

AC XY:

146

AN XY:

363128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35173

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.000945

AC:

AN:

53973

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000407

AC:

343

AN:

841938

Other (OTH)

AF:

0.000195

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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

100

<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:

0.000135

AC:

AN:

111200

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30622

American (AMR)

AF:

0.00

AC:

AN:

10498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.000766

AC:

AN:

2611

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000246

AC:

AN:

52930

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.000304

Hom.:

Bravo

AF:

0.000144

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

BCOR-related disorder (1)

not provided (1)

not specified (1)

Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.7

(source)

DANN

Benign

0.65

PhyloP100

-0.052

Mutation Taster

=99/1

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.

rs753786462

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over