rs139802143

Positions:

chrX-40074938-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001123385.2(BCOR):c.408C>T(p.Ala136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000467 in 1,208,860 control chromosomes in the GnomAD database, including 3 homozygotes. There are 151 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., 75 hem., cov: 22)

Exomes 𝑓: 0.00027 ( 2 hom. 76 hem. )

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.175

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant X-40074938-G-A is Benign according to our data. Variant chrX-40074938-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210521.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}. Variant chrX-40074938-G-A is described in Lovd as [Likely_benign]. Variant chrX-40074938-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.175 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00242 (268/110710) while in subpopulation AFR AF= 0.00848 (258/30430). AF 95% confidence interval is 0.00763. There are 1 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 75 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.408C>T	p.Ala136=	synonymous_variant	4/15	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.408C>T	p.Ala136=	synonymous_variant	4/15	1	NM_001123385.2	ENSP00000367705	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

268

AN:

110657

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

AN XY:

32885

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000730

AC:

134

AN:

183444

Hom.:

AF XY:

0.000619

AC XY:

AN XY:

67878

show subpopulations

Gnomad AFR exome

AF:

0.00950

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000270

AC:

296

AN:

1098150

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

363506

show subpopulations

Gnomad4 AFR exome

AF:

0.00939

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.0000740

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.000477

GnomAD4 genome

AF:

0.00242

AC:

268

AN:

110710

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

AN XY:

32948

show subpopulations

Gnomad4 AFR

AF:

0.00848

Gnomad4 AMR

AF:

0.000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00287

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 08, 2014	- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

History of neurodevelopmental disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2011

This alteration is classified as likely benign based on a combination of the following: 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. -

Oculofaciocardiodental syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.15

DANN

Benign

0.59

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

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