rs1555918870

Variant names:

• chrX-40073802-C-T
• rs1555918870
• NM_001123385.2:c.1544G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123385.2(BCOR):​c.1544G>A​(p.Ser515Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: BCOR NM_001123385.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20295438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.1544G>A	p.Ser515Asn	missense_variant	Exon 4 of 15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.1544G>A	p.Ser515Asn	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098188 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 1 AN XY: 363542

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

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40503

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842120

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

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;.;T;.;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.67	.;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;L;L;.
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.037
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Benign	0.33	T;T;T;T;.
Polyphen		0.52	P;P;B;P;.
Vest4		0.31
MutPred		0.20		Loss of phosphorylation at S515 (P = 0.0359);Loss of phosphorylation at S515 (P = 0.0359);Loss of phosphorylation at S515 (P = 0.0359);Loss of phosphorylation at S515 (P = 0.0359);Loss of phosphorylation at S515 (P = 0.0359);
MVP		0.36
MPC		0.30
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.42
gMVP		0.39
Mutation Taster		=92/8	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: rs1555918870; hg19: chrX-39933055;