rs78992023

Positions:

chrX-40052404-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378444.9(BCOR):c.4977-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,205,271 control chromosomes in the GnomAD database, including 14,154 homozygotes. There are 70,182 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 1280 hom., 4989 hem., cov: 22)

Exomes 𝑓: 0.18 ( 12874 hom. 65193 hem. )

Consequence

BCOR
ENST00000378444.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003587

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.71

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-40052404-C-A is Benign according to our data. Variant chrX-40052404-C-A is described in ClinVar as [Benign]. Clinvar id is 95772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40052404-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.4977-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.4977-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001123385.2	ENSP00000367705	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

18570

AN:

110308

Hom.:

1282

Cov.:

AF XY:

0.153

AC XY:

4988

AN XY:

32584

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.000559

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.149

AC:

27117

AN:

181988

Hom.:

1467

AF XY:

0.154

AC XY:

10312

AN XY:

67024

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0765

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.00108

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.181

AC:

197935

AN:

1094910

Hom.:

12874

Cov.:

AF XY:

0.181

AC XY:

65193

AN XY:

360718

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.0830

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.000564

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.168

AC:

18561

AN:

110361

Hom.:

1280

Cov.:

AF XY:

0.153

AC XY:

4989

AN XY:

32647

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.000560

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.188

Hom.:

1651

Bravo

AF:

0.169

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 06, 2014	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2014

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.27

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over