rs146007249

Positions:

chrX-40055429-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001123385.2(BCOR):c.4680G>A(p.Thr1560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,208,856 control chromosomes in the GnomAD database, including 1 homozygotes. There are 94 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 42 hem., cov: 23)

Exomes 𝑓: 0.00017 ( 1 hom. 52 hem. )

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.36

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-40055429-C-T is Benign according to our data. Variant chrX-40055429-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40055429-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00132 (148/112223) while in subpopulation AFR AF= 0.00446 (138/30934). AF 95% confidence interval is 0.00386. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 42 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2 linkuse as main transcript	c.4680G>A	p.Thr1560=	synonymous_variant	12/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9 linkuse as main transcript	c.4680G>A	p.Thr1560=	synonymous_variant	12/15	1	NM_001123385.2	P2	Q6W2J9-1

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

148

AN:

112166

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

34330

show subpopulations

Gnomad AFR

AF:

0.00447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.00

Gnomad OTH

AF:

0.000662

GnomAD3 exomes

AF:

0.000425

AC:

AN:

183474

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

67920

show subpopulations

Gnomad AFR exome

AF:

0.00555

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

190

AN:

1096633

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

362023

show subpopulations

Gnomad4 AFR exome

AF:

0.00402

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000726

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00132

AC:

148

AN:

112223

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

34397

show subpopulations

Gnomad4 AFR

AF:

0.00446

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000654

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 13, 2016

- -

Oculofaciocardiodental syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2024

- -

Microphthalmia, syndromic 1;C1846265:Oculofaciocardiodental syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.6

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)

0.15

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