rs1555913337

Variant names:

• chrX-40054272-ATAGAAGTCCCAAGTGC-A
• rs1555913337
• NM_001123385.2:c.4787_4802delGCACTTGGGACTTCTA

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001123385.2(BCOR):​c.4787_4802delGCACTTGGGACTTCTA​(p.Gly1596ValfsTer17) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCOR NM_001123385.2 frameshift
• Clinical Significance: Other O:1
• Conservation: PhyloP100: 8.88
• Publications: 0 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: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.4787_4802delGCACTTGGGACTTCTA	p.Gly1596ValfsTer17	frameshift	Exon 13 of 15	NP_001116857.1
	BCOR	NM_001437510.1		c.4787_4802delGCACTTGGGACTTCTA	p.Gly1596ValfsTer17	frameshift	Exon 13 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.4733_4748delGCACTTGGGACTTCTA	p.Gly1578ValfsTer17	frameshift	Exon 12 of 14	NP_001425136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.4787_4802delGCACTTGGGACTTCTA	p.Gly1596ValfsTer17	frameshift	Exon 13 of 15	ENSP00000367705.4
	BCOR	ENST00000397354.7	TSL:1	c.4685_4700delGCACTTGGGACTTCTA	p.Gly1562ValfsTer17	frameshift	Exon 13 of 15	ENSP00000380512.3
	BCOR	ENST00000378455.8	TSL:1	c.4631_4646delGCACTTGGGACTTCTA	p.Gly1544ValfsTer17	frameshift	Exon 12 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance:

Submissions summary: Other:1

Revision:

Submissions by phenotype

Adenoid cystic carcinoma Other:1

Nov 13, 2024

Genome Sciences Centre, British Columbia Cancer Agency

Significance:

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555913337; hg19: chrX-39913525;