rs1459702445

Variant names:

• chrX-40074867-A-G
• rs1459702445
• NM_001123385.2:c.479T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001123385.2(BCOR):​c.479T>C​(p.Val160Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,197 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.68
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000182 (2/1098197) while in subpopulation MID AF = 0.000483 (2/4137). AF 95% confidence interval is 0.0000851. There are 0 homozygotes in GnomAdExome4. There are 0 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.

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.479T>C	p.Val160Ala	missense	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.479T>C	p.Val160Ala	missense	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.479T>C	p.Val160Ala	missense	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.479T>C	p.Val160Ala	missense	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.479T>C	p.Val160Ala	missense	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.479T>C	p.Val160Ala	missense	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183314 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098197 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 363551

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40527

Middle Eastern (MID) AF: 0.000483 AC: 2 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842092

Other (OTH) AF: 0.00 AC: 0 AN: 46095

GnomAD4 genome Cov.: 23

Alfa AF: 0.000111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.40		Gain of disorder (P = 0.0169)
MVP		0.85
MPC		1.0
ClinPred		0.54	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.56
Mutation Taster		=81/19	polymorphism

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: rs1459702445; hg19: chrX-39934120;