Genetic Variant BCOR:c.*300delA (chrX-40051808-AT-A) – 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.*300delA 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 0.00056 ( 0 hom., 12 hem., cov: 18)

Exomes 𝑓: 0.00028 ( 0 hom. 3 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 = 0.000558 (61/109294) while in subpopulation AFR AF = 0.0019 (57/30007). AF 95% confidence interval is 0.00151. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 12 XLD,XL gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

109251

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00190

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000684

GnomAD4 exome

AF:

0.000275

AC:

AN:

116332

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

29574

show subpopulations

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

African (AFR)

AF:

0.00187

AC:

AN:

4269

American (AMR)

AF:

0.000598

AC:

AN:

5016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4822

East Asian (EAS)

AF:

0.0000840

AC:

AN:

11910

South Asian (SAS)

AF:

0.00

AC:

AN:

2384

European-Finnish (FIN)

AF:

0.000769

AC:

AN:

5201

Middle Eastern (MID)

AF:

0.00

AC:

AN:

529

European-Non Finnish (NFE)

AF:

0.000190

AC:

AN:

73708

Other (OTH)

AF:

0.000235

AC:

AN:

8493

⚠️ 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: 0.294

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000558

AC:

AN:

109294

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

31866

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

30007

American (AMR)

AF:

0.000196

AC:

AN:

10191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2604

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5665

Middle Eastern (MID)

AF:

0.00

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

52354

Other (OTH)

AF:

0.000675

AC:

AN:

1482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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-A

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