Genetic Variant BCOR:c.*300dupA (chrX-40051808-A-AT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001123385.2(BCOR):c.*300dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., 21 hem., cov: 18)

Exomes 𝑓: 0.0035 ( 0 hom. 11 hem. )

Consequence

BCOR
NM_001123385.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000741 (81/109269) while in subpopulation AFR AF = 0.001 (30/30001). AF 95% confidence interval is 0.000719. There are 0 homozygotes in GnomAd4. There are 21 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 21 XLD,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.*300dupA		3_prime_UTR_variant	Exon 15 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.*300dupA		3_prime_UTR_variant	Exon 15 of 15	1	NM_001123385.2	ENSP00000367705.4		Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

AN:

109227

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00212

Gnomad MID

AF:

0.00866

Gnomad NFE

AF:

0.000669

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00347

AC:

395

AN:

113671

Hom.:

Cov.:

AF XY:

0.000395

AC XY:

AN XY:

27845

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00312

AC:

AN:

4164

American (AMR)

AF:

0.00344

AC:

AN:

4939

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

4696

East Asian (EAS)

AF:

0.000930

AC:

AN:

11829

South Asian (SAS)

AF:

0.00346

AC:

AN:

2312

European-Finnish (FIN)

AF:

0.00684

AC:

AN:

5118

Middle Eastern (MID)

AF:

0.00396

AC:

AN:

505

European-Non Finnish (NFE)

AF:

0.00397

AC:

285

AN:

71793

Other (OTH)

AF:

0.00192

AC:

AN:

8315

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000741

AC:

AN:

109269

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

31843

show subpopulations

African (AFR)

AF:

0.00100

AC:

AN:

30001

American (AMR)

AF:

0.000196

AC:

AN:

10191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2606

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2575

European-Finnish (FIN)

AF:

0.00212

AC:

AN:

5660

Middle Eastern (MID)

AF:

0.00957

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.000669

AC:

AN:

52340

Other (OTH)

AF:

0.00

AC:

AN:

1481

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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X-40051808-AT-ATT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over