rs61744882

chrX-40075123-T-AchrX-40075123-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001123385.2(BCOR):c.223A>T(p.Thr75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000894 in 1,208,035 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 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 0.00050 (0 hom., 14 hem., cov: 21)
  • Exomes 𝑓: 0.000048 (0 hom. 15 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025066644).
• BP6: Variant X-40075123-T-A is Benign according to our data. Variant chrX-40075123-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 581701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000497 (55/110602) while in subpopulation AFR AF= 0.00178 (54/30336). AF 95% confidence interval is 0.0014. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.223A>T	p.Thr75Ser	missense_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.223A>T	p.Thr75Ser	missense_variant	4/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.000507 AC: 56 AN: 110550 Hom.: 0 Cov.: 21 AF XY: 0.000427 AC XY: 14 AN XY: 32790

Gnomad AFR AF: 0.00182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000960

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: 0.000106 AC: 19 AN: 179316 Hom.: 0 AF XY: 0.0000155 AC XY: 1 AN XY: 64698

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00

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: 0.0000483 AC: 53 AN: 1097433 Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 15 AN XY: 362853

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00

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: 0.0000217

GnomAD4 genome AF: 0.000497 AC: 55 AN: 110602 Hom.: 0 Cov.: 21 AF XY: 0.000426 AC XY: 14 AN XY: 32852

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.0000959

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: 0.0000378 Hom.: 0

Bravo AF: 0.000582

ESP6500AA AF: 0.00130 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oculofaciocardiodental syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	8.4
Dann	Benign	0.96
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.025	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.43	N;N;N;N;.
MutationTaster	Benign	0.55	N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.30	N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.30	T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;T;.
Polyphen		0.31	B;B;B;B;.
Vest4		0.081
MutPred		0.20		Loss of catalytic residue at T75 (P = 0.0511);Loss of catalytic residue at T75 (P = 0.0511);Loss of catalytic residue at T75 (P = 0.0511);Loss of catalytic residue at T75 (P = 0.0511);Loss of catalytic residue at T75 (P = 0.0511);
MVP		0.65
MPC		0.24
ClinPred		0.027	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.25

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: rs61744882; hg19: chrX-39934376;