NM_001123385.2:c.574G>C

Variant names:

• chrX-40074772-C-G
• rs1555919769
• NM_001123385.2:c.574G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001123385.2(BCOR):​c.574G>C​(p.Val192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,098,261 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 0 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• Publications: 0 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: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31311655).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.574G>C	p.Val192Leu	missense	Exon 4 of 15	NP_001116857.1
	BCOR	NM_001437510.1		c.574G>C	p.Val192Leu	missense	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.574G>C	p.Val192Leu	missense	Exon 4 of 14	NP_001425136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.574G>C	p.Val192Leu	missense	Exon 4 of 15	ENSP00000367705.4
	BCOR	ENST00000397354.7	TSL:1	c.574G>C	p.Val192Leu	missense	Exon 4 of 15	ENSP00000380512.3
	BCOR	ENST00000378455.8	TSL:1	c.574G>C	p.Val192Leu	missense	Exon 4 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000728 AC: 8 AN: 1098261 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 363615

African (AFR) AF: 0.00 AC: 0 AN: 26403

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: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000950 AC: 8 AN: 842145

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 12, 2016

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.58	N
PhyloP100		2.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.14
Sift	Benign	0.20	T
Sift4G	Benign	0.94	T
Polyphen		0.94	P
Vest4		0.15
MutPred		0.22		Loss of sheet (P = 0.0457)
MVP		0.84
MPC		0.92
ClinPred		0.54	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.19
gMVP		0.40
Mutation Taster		=83/17	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: rs1555919769; hg19: chrX-39934025;