rs3810693

chrX-40072655-C-AchrX-40072655-C-GchrX-40072655-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001123385.2(BCOR):c.2691G>T(p.Ser897=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,210,445 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 85 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S897S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., 19 hem., cov: 24)
  • Exomes 𝑓: 0.00018 (0 hom. 66 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-40072655-C-A is Benign according to our data. Variant chrX-40072655-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2182685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.51 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCOR	NM_001123385.2	c.2691G>T	p.Ser897=	synonymous_variant	4/15	ENST00000378444.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCOR	ENST00000378444.9	c.2691G>T	p.Ser897=	synonymous_variant	4/15	1	NM_001123385.2	P2

Frequencies

GnomAD3 genomes AF: 0.000303 AC: 34 AN: 112184 Hom.: 0 Cov.: 24 AF XY: 0.000553 AC XY: 19 AN XY: 34350

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.00394

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.000662

GnomAD3 exomes AF: 0.000376 AC: 69 AN: 183433 Hom.: 0 AF XY: 0.000354 AC XY: 24 AN XY: 67883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000419

Gnomad FIN exome AF: 0.00294

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000182 AC: 200 AN: 1098206 Hom.: 0 Cov.: 30 AF XY: 0.000182 AC XY: 66 AN XY: 363566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.0000891

Gnomad4 OTH exome AF: 0.000174

GnomAD4 genome AF: 0.000303 AC: 34 AN: 112239 Hom.: 0 Cov.: 24 AF XY: 0.000552 AC XY: 19 AN XY: 34415

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000367

Gnomad4 FIN AF: 0.00394

Gnomad4 NFE AF: 0.000150

Gnomad4 OTH AF: 0.000654

Alfa AF: 0.0000364 Hom.: 1

Bravo AF: 0.0000491

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

BCOR: BP4, BP7, BS2 -

Oculofaciocardiodental syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.037
Dann	Benign	0.50
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs3810693; hg19: chrX-39931908;