X-40051808-AT-A

Variant names:

• chrX-40051808-AT-A
• rs35289701
• NM_001123385.2:c.*300delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 2 publications found

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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.*300delA		3_prime_UTR	Exon 15 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.*300delA		3_prime_UTR	Exon 15 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.*300delA		3_prime_UTR	Exon 14 of 14	NP_001425136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.*300delA		3_prime_UTR	Exon 15 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.*300delA		3_prime_UTR	Exon 15 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.*300delA		3_prime_UTR	Exon 14 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 61 AN: 109251 Hom.: 0 Cov.: 18

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: 32 AN: 116332 Hom.: 0 Cov.: 0 AF XY: 0.000101 AC XY: 3 AN XY: 29574

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

African (AFR) AF: 0.00187 AC: 8 AN: 4269

American (AMR) AF: 0.000598 AC: 3 AN: 5016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4822

East Asian (EAS) AF: 0.0000840 AC: 1 AN: 11910

South Asian (SAS) AF: 0.00 AC: 0 AN: 2384

European-Finnish (FIN) AF: 0.000769 AC: 4 AN: 5201

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 529

European-Non Finnish (NFE) AF: 0.000190 AC: 14 AN: 73708

Other (OTH) AF: 0.000235 AC: 2 AN: 8493

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000558 AC: 61 AN: 109294 Hom.: 0 Cov.: 18 AF XY: 0.000377 AC XY: 12 AN XY: 31866

African (AFR) AF: 0.00190 AC: 57 AN: 30007

American (AMR) AF: 0.000196 AC: 2 AN: 10191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2604

East Asian (EAS) AF: 0.00 AC: 0 AN: 3548

South Asian (SAS) AF: 0.00 AC: 0 AN: 2576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5665

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52354

Other (OTH) AF: 0.000675 AC: 1 AN: 1482

Alfa AF: 0.00 Hom.: 384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35289701; hg19: chrX-39911061;