X-40073567-G-T

Variant names:

• chrX-40073567-G-T
• rs17145652
• NM_001123385.2:c.1779C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001123385.2(BCOR):​c.1779C>A​(p.Ser593Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,211,089 control chromosomes in the GnomAD database, including 55 homozygotes. There are 1,077 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S593S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., 490 hem., cov: 25)
  • Exomes 𝑓: 0.0019 (35 hom. 587 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.70
• Publications: 3 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-40073567-G-T is Benign according to our data. Variant chrX-40073567-G-T is described in ClinVar as Benign. ClinVar VariationId is 128523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

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.1779C>A	p.Ser593Ser	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1779C>A	p.Ser593Ser	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.1779C>A	p.Ser593Ser	synonymous	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.1779C>A	p.Ser593Ser	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1779C>A	p.Ser593Ser	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1779C>A	p.Ser593Ser	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 1608 AN: 113066 Hom.: 20 Cov.: 25

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00601

Gnomad ASJ AF: 0.0128

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000718

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.0111

GnomAD2 exomes AF: 0.00484 AC: 886 AN: 182959 AF XY: 0.00360

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00190 AC: 2084 AN: 1097970 Hom.: 35 Cov.: 31 AF XY: 0.00162 AC XY: 587 AN XY: 363362

African (AFR) AF: 0.0528 AC: 1395 AN: 26403

American (AMR) AF: 0.00298 AC: 105 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 263 AN: 19386

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

South Asian (SAS) AF: 0.0000739 AC: 4 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40254

Middle Eastern (MID) AF: 0.00314 AC: 13 AN: 4136

European-Non Finnish (NFE) AF: 0.000125 AC: 105 AN: 842134

Other (OTH) AF: 0.00432 AC: 199 AN: 46096

GnomAD4 genome AF: 0.0143 AC: 1612 AN: 113119 Hom.: 20 Cov.: 25 AF XY: 0.0139 AC XY: 490 AN XY: 35263

African (AFR) AF: 0.0475 AC: 1481 AN: 31190

American (AMR) AF: 0.00601 AC: 65 AN: 10820

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 34 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3578

South Asian (SAS) AF: 0.000720 AC: 2 AN: 2777

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000244 AC: 13 AN: 53369

Other (OTH) AF: 0.0110 AC: 17 AN: 1544

Alfa AF: 0.00244 Hom.: 24

Bravo AF: 0.0171

EpiCase AF: 0.000709

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	History of neurodevelopmental disorder (1)
-	-	1	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.53
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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: rs17145652; hg19: chrX-39932820;