rs1057522572

Variant names:

• chrX-40052203-T-C
• rs1057522572
• NM_001123385.2:c.5174A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-40052203-T-C
• chrX-40052203-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001123385.2(BCOR):​c.5174A>G​(p.Asp1725Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,097,763 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1725A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52
• 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 XL,Unknown gene

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.5174A>G	p.Asp1725Gly	missense	Exon 15 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.5174A>G	p.Asp1725Gly	missense	Exon 15 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.5120A>G	p.Asp1707Gly	missense	Exon 14 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.5174A>G	p.Asp1725Gly	missense	Exon 15 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.5072A>G	p.Asp1691Gly	missense	Exon 15 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.5018A>G	p.Asp1673Gly	missense	Exon 14 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097763 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 363133

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54029

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841823

Other (OTH) AF: 0.00 AC: 0 AN: 46081

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.69	P
Vest4		0.68
MutPred		0.63		Loss of stability (P = 0.0639)
MVP		0.66
MPC		0.43
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.90
gMVP		0.75
Mutation Taster		=33/67	disease causing

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: rs1057522572; hg19: chrX-39911456;