rs6520618

chrX-40073654-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001123385.2(BCOR):c.1692A>G(p.Ala564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,210,479 control chromosomes in the GnomAD database, including 26,452 homozygotes. There are 71,066 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8378 hom., 11497 hem., cov: 25)
  • Exomes 𝑓: 0.16 (18074 hom. 59569 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -5.09

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-40073654-T-C is Benign according to our data. Variant chrX-40073654-T-C is described in ClinVar as [Benign]. Clinvar id is 95766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40073654-T-C is described in Lovd as [Likely_benign]. Variant chrX-40073654-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.1692A>G	p.Ala564=	synonymous_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.1692A>G	p.Ala564=	synonymous_variant	4/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 38174 AN: 112365 Hom.: 8372 Cov.: 25 AF XY: 0.331 AC XY: 11437 AN XY: 34557

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.253 AC: 46239 AN: 182781 Hom.: 7228 AF XY: 0.243 AC XY: 16370 AN XY: 67309

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.707

Gnomad SAS exome AF: 0.400

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.157 AC: 172780 AN: 1098058 Hom.: 18074 Cov.: 33 AF XY: 0.164 AC XY: 59569 AN XY: 363428

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.340 AC: 38243 AN: 112421 Hom.: 8378 Cov.: 25 AF XY: 0.332 AC XY: 11497 AN XY: 34623

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.300

Alfa AF: 0.160 Hom.: 10047

Bravo AF: 0.374

EpiCase AF: 0.111

EpiControl AF: 0.109

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 30, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Oculofaciocardiodental syndrome Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.012
Dann	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6520618; hg19: chrX-39932907; COSMIC: COSV60701032; COSMIC: COSV60701032;