X-40072832-G-T

Variant names:

• chrX-40072832-G-T
• rs147497014
• NM_001123385.2:c.2514C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001123385.2(BCOR):​c.2514C>A​(p.Pro838Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,209,738 control chromosomes in the GnomAD database, including 1 homozygotes. There are 708 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., 21 hem., cov: 23)
  • Exomes 𝑓: 0.0020 (1 hom. 687 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.326
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-40072832-G-T is Benign according to our data. Variant chrX-40072832-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 166749.
• BP7: Synonymous conserved (PhyloP=0.326 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00077 (86/111663) while in subpopulation NFE AF = 0.00139 (74/53093). AF 95% confidence interval is 0.00114. There are 0 homozygotes in GnomAd4. There are 21 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 21 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.2514C>A	p.Pro838Pro	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.2514C>A	p.Pro838Pro	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.2514C>A	p.Pro838Pro	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.2514C>A	p.Pro838Pro	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.2514C>A	p.Pro838Pro	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.2514C>A	p.Pro838Pro	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.000770 AC: 86 AN: 111663 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00139

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000682 AC: 125 AN: 183208 AF XY: 0.000664

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.00196 AC: 2155 AN: 1098075 Hom.: 1 Cov.: 31 AF XY: 0.00189 AC XY: 687 AN XY: 363435

African (AFR) AF: 0.000379 AC: 10 AN: 26401

American (AMR) AF: 0.0000852 AC: 3 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.0000741 AC: 3 AN: 40485

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4117

European-Non Finnish (NFE) AF: 0.00247 AC: 2084 AN: 842043

Other (OTH) AF: 0.00117 AC: 54 AN: 46090

GnomAD4 genome AF: 0.000770 AC: 86 AN: 111663 Hom.: 0 Cov.: 23 AF XY: 0.000621 AC XY: 21 AN XY: 33825

African (AFR) AF: 0.000391 AC: 12 AN: 30652

American (AMR) AF: 0.00 AC: 0 AN: 10598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2583

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6099

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00139 AC: 74 AN: 53093

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.000565 Hom.: 4

Bravo AF: 0.000748

EpiCase AF: 0.00115

EpiControl AF: 0.00119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	-	1	not specified (1)
-	-	1	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	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: rs147497014; hg19: chrX-39932085;