rs6520618

Variant names:

• chrX-40073654-T-C
• rs6520618
• NM_001123385.2:c.1692A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001123385.2(BCOR):​c.1692A>G​(p.Ala564Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,210,479 control chromosomes in the GnomAD database, including 26,452 homozygotes. There are 71,066 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8378 hom., 11497 hem., cov: 25)
  • Exomes 𝑓: 0.16 (18074 hom. 59569 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -5.09
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 2

  Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen, Ambry Genetics
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-40073654-T-C is Benign according to our data. Variant chrX-40073654-T-C is described in ClinVar as Benign. ClinVar VariationId is 95766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123385.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 14	NP_001425136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1692A>G	p.Ala564Ala	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 38174 AN: 112365 Hom.: 8372 Cov.: 25

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.253 AC: 46239 AN: 182781 AF XY: 0.243

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.157 AC: 172780 AN: 1098058 Hom.: 18074 Cov.: 33 AF XY: 0.164 AC XY: 59569 AN XY: 363428

African (AFR) AF: 0.820 AC: 21650 AN: 26402

American (AMR) AF: 0.203 AC: 7160 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 3895 AN: 19385

East Asian (EAS) AF: 0.654 AC: 19744 AN: 30197

South Asian (SAS) AF: 0.400 AC: 21645 AN: 54148

European-Finnish (FIN) AF: 0.114 AC: 4617 AN: 40429

Middle Eastern (MID) AF: 0.216 AC: 892 AN: 4131

European-Non Finnish (NFE) AF: 0.0986 AC: 82991 AN: 842089

Other (OTH) AF: 0.221 AC: 10186 AN: 46089

GnomAD4 genome AF: 0.340 AC: 38243 AN: 112421 Hom.: 8378 Cov.: 25 AF XY: 0.332 AC XY: 11497 AN XY: 34623

African (AFR) AF: 0.800 AC: 24696 AN: 30852

American (AMR) AF: 0.228 AC: 2465 AN: 10801

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 530 AN: 2656

East Asian (EAS) AF: 0.684 AC: 2390 AN: 3494

South Asian (SAS) AF: 0.406 AC: 1119 AN: 2754

European-Finnish (FIN) AF: 0.122 AC: 756 AN: 6219

Middle Eastern (MID) AF: 0.256 AC: 55 AN: 215

European-Non Finnish (NFE) AF: 0.104 AC: 5552 AN: 53225

Other (OTH) AF: 0.300 AC: 461 AN: 1535

Alfa AF: 0.200 Hom.: 14737

Bravo AF: 0.374

EpiCase AF: 0.111

EpiControl AF: 0.109

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Oculofaciocardiodental syndrome (3)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.19
PhyloP100		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6520618; hg19: chrX-39932907; COSMIC: COSV60701032; COSMIC: COSV60701032;