X-40051808-AT-ATT

Variant names:

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

Variant summary

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

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
• 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 = 0.000741 (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 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.*300dupA		3_prime_UTR	Exon 15 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.*300dupA		3_prime_UTR	Exon 15 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.*300dupA		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.*300dupA		3_prime_UTR	Exon 15 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.*300dupA		3_prime_UTR	Exon 15 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.*300dupA		3_prime_UTR	Exon 14 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.000742 AC: 81 AN: 109227 Hom.: 0 Cov.: 18

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.: 0 Cov.: 0 AF XY: 0.000395 AC XY: 11 AN XY: 27845

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

African (AFR) AF: 0.00312 AC: 13 AN: 4164

American (AMR) AF: 0.00344 AC: 17 AN: 4939

Ashkenazi Jewish (ASJ) AF: 0.00170 AC: 8 AN: 4696

East Asian (EAS) AF: 0.000930 AC: 11 AN: 11829

South Asian (SAS) AF: 0.00346 AC: 8 AN: 2312

European-Finnish (FIN) AF: 0.00684 AC: 35 AN: 5118

Middle Eastern (MID) AF: 0.00396 AC: 2 AN: 505

European-Non Finnish (NFE) AF: 0.00397 AC: 285 AN: 71793

Other (OTH) AF: 0.00192 AC: 16 AN: 8315

⚠️ 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: 0.000741 AC: 81 AN: 109269 Hom.: 0 Cov.: 18 AF XY: 0.000659 AC XY: 21 AN XY: 31843

African (AFR) AF: 0.00100 AC: 30 AN: 30001

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2606

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 2575

European-Finnish (FIN) AF: 0.00212 AC: 12 AN: 5660

Middle Eastern (MID) AF: 0.00957 AC: 2 AN: 209

European-Non Finnish (NFE) AF: 0.000669 AC: 35 AN: 52340

Other (OTH) AF: 0.00 AC: 0 AN: 1481

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;