rs145327925

chrX-40064425-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001123385.2(BCOR):c.3413T>C(p.Val1138Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,210,794 control chromosomes in the GnomAD database, including 2 homozygotes. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (1 hom., 31 hem., cov: 24)
  • Exomes 𝑓: 0.000084 (1 hom. 23 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0790

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061370134).
• BP6: Variant X-40064425-A-G is Benign according to our data. Variant chrX-40064425-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 95769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40064425-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000782 (88/112567) while in subpopulation AFR AF= 0.00277 (86/31023). AF 95% confidence interval is 0.0023. There are 1 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.3413T>C	p.Val1138Ala	missense_variant	7/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.3413T>C	p.Val1138Ala	missense_variant	7/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.000791 AC: 89 AN: 112515 Hom.: 1 Cov.: 24 AF XY: 0.000922 AC XY: 32 AN XY: 34701

Gnomad AFR AF: 0.00281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

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: 0.00

GnomAD3 exomes AF: 0.000290 AC: 53 AN: 183020 Hom.: 0 AF XY: 0.000237 AC XY: 16 AN XY: 67516

Gnomad AFR exome AF: 0.00350

Gnomad AMR exome AF: 0.000255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000838 AC: 92 AN: 1098227 Hom.: 1 Cov.: 32 AF XY: 0.0000633 AC XY: 23 AN XY: 363581

Gnomad4 AFR exome AF: 0.00288

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000174

GnomAD4 genome AF: 0.000782 AC: 88 AN: 112567 Hom.: 1 Cov.: 24 AF XY: 0.000892 AC XY: 31 AN XY: 34763

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.000185

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: 0.00

Alfa AF: 0.0000621 Hom.: 1

Bravo AF: 0.000842

ESP6500AA AF: 0.00417 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000313 AC: 38

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 21, 2014

- -

Oculofaciocardiodental syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.89
Cadd	Benign	12
Dann	Benign	0.94
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.64	T;T;.;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0061	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.10	N;N;N;N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.26	T;T;T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;T;T;.
Polyphen		0.0	.;.;B;B;B;B;.
Vest4		0.099, 0.067, 0.091, 0.082, 0.065
MVP		0.39
MPC		0.32
ClinPred		0.0090	T
GERP RS		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.076

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: rs145327925; hg19: chrX-39923678;