rs1555919769

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.574G>C	p.Val192Leu	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.574G>C	p.Val192Leu	missense_variant	Exon 4 of 15	1	NM_001123385.2	ENSP00000367705.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000950

Gnomad4 OTH exome AF: 0.00

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

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Computational scores

Source: dbNSFP v4.3

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;.;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	.;D;D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.58	N;N;N;N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.56	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.94	T;T;T;T;.
Polyphen		0.94	P;P;P;P;.
Vest4		0.15
MutPred		0.22		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555919769; hg19: chrX-39934025;