X-40073567-G-T

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.1779C>A(p.Ser593=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,211,089 control chromosomes in the GnomAD database, including 55 homozygotes. There are 1,077 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S593S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., 490 hem., cov: 25)
  • Exomes 𝑓: 0.0019 (35 hom. 587 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.70

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=-0.83).
• BP6: Variant X-40073567-G-T is Benign according to our data. Variant chrX-40073567-G-T is described in ClinVar as [Benign]. Clinvar id is 128523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.1779C>A	p.Ser593=	synonymous_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.1779C>A	p.Ser593=	synonymous_variant	4/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 1608 AN: 113066 Hom.: 20 Cov.: 25 AF XY: 0.0138 AC XY: 485 AN XY: 35200

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00601

Gnomad ASJ AF: 0.0128

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000718

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.0111

GnomAD3 exomes AF: 0.00484 AC: 886 AN: 182959 Hom.: 13 AF XY: 0.00360 AC XY: 243 AN XY: 67457

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00190 AC: 2084 AN: 1097970 Hom.: 35 Cov.: 31 AF XY: 0.00162 AC XY: 587 AN XY: 363362

Gnomad4 AFR exome AF: 0.0528

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000739

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000125

Gnomad4 OTH exome AF: 0.00432

GnomAD4 genome AF: 0.0143 AC: 1612 AN: 113119 Hom.: 20 Cov.: 25 AF XY: 0.0139 AC XY: 490 AN XY: 35263

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.0128

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000720

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.0110

Alfa AF: 0.00244 Hom.: 24

Bravo AF: 0.0171

EpiCase AF: 0.000709

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

History of neurodevelopmental disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2014

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Oculofaciocardiodental syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.23
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17145652; hg19: chrX-39932820;