rs769057299

chrX-40064347-C-T

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.3491G>A(p.Arg1164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000603 in 1,211,134 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000061 (0 hom. 14 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.79

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=0.018598765).
• BP6: Variant X-40064347-C-T is Benign according to our data. Variant chrX-40064347-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 533720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000061 (67/1098174) while in subpopulation AMR AF= 0.00173 (61/35207). AF 95% confidence interval is 0.00138. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.3491G>A	p.Arg1164Gln	missense_variant	7/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.3491G>A	p.Arg1164Gln	missense_variant	7/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 6 AN: 112960 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35098

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000462

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000336 AC: 61 AN: 181566 Hom.: 0 AF XY: 0.000209 AC XY: 14 AN XY: 67126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00215

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: 0.0000125

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000610 AC: 67 AN: 1098174 Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 14 AN XY: 363536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00173

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: 0.00000475

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome AF: 0.0000531 AC: 6 AN: 112960 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35098

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000462

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000422 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.000305 AC: 37

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BCOR-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 02, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Oculofaciocardiodental syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	22
Dann	Pathogenic	1.0
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;.;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.019	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.78	D;N;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.078	T;T;T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T;T;.
Polyphen		0.97, 0.98	.;.;D;D;D;D;.
Vest4		0.22, 0.23, 0.24, 0.43, 0.23
MutPred		0.18		.;.;Gain of ubiquitination at K1167 (P = 0.0212);.;Gain of ubiquitination at K1167 (P = 0.0212);Gain of ubiquitination at K1167 (P = 0.0212);Gain of ubiquitination at K1167 (P = 0.0212);
MVP		0.45
MPC		0.44
ClinPred		0.12	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.16

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: rs769057299; hg19: chrX-39923600;