rs5917933

Variant names:

• chrX-40074086-A-G
• rs5917933
• NM_001123385.2:c.1260T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-40074086-A-G
• chrX-40074086-A-T
• chrX-40074086-A-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001123385.2(BCOR):​c.1260T>C​(p.Asp420Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (31517 hom., 30649 hem., cov: 24)
  • Exomes 𝑓: 0.88 (285959 hom. 317776 hem.)
  • Failed GnomAD Quality Control
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.0430
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-40074086-A-G is Benign according to our data. Variant chrX-40074086-A-G is described in ClinVar as Benign. ClinVar VariationId is 95764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.043 with no splicing effect.

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.1260T>C	p.Asp420Asp	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1260T>C	p.Asp420Asp	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.1260T>C	p.Asp420Asp	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.1260T>C	p.Asp420Asp	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1260T>C	p.Asp420Asp	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1260T>C	p.Asp420Asp	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.901 AC: 100569 AN: 111671 Hom.: 31517 Cov.: 24

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.890

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.899

GnomAD2 exomes AF: 0.897 AC: 163861 AN: 182605 AF XY: 0.885

Gnomad AFR exome AF: 0.924

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.973

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.881

Gnomad OTH exome AF: 0.890

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.879 AC: 965553 AN: 1097944 Hom.: 285959 Cov.: 76 AF XY: 0.875 AC XY: 317776 AN XY: 363318

African (AFR) AF: 0.924 AC: 24398 AN: 26401

American (AMR) AF: 0.951 AC: 33493 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 17443 AN: 19386

East Asian (EAS) AF: 0.982 AC: 29664 AN: 30200

South Asian (SAS) AF: 0.774 AC: 41882 AN: 54126

European-Finnish (FIN) AF: 0.937 AC: 37881 AN: 40432

Middle Eastern (MID) AF: 0.861 AC: 3560 AN: 4136

European-Non Finnish (NFE) AF: 0.875 AC: 736645 AN: 841971

Other (OTH) AF: 0.881 AC: 40587 AN: 46088

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.901 AC: 100630 AN: 111723 Hom.: 31517 Cov.: 24 AF XY: 0.905 AC XY: 30649 AN XY: 33883

African (AFR) AF: 0.922 AC: 28413 AN: 30810

American (AMR) AF: 0.925 AC: 9856 AN: 10653

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 2410 AN: 2648

East Asian (EAS) AF: 0.971 AC: 3405 AN: 3506

South Asian (SAS) AF: 0.784 AC: 2101 AN: 2680

European-Finnish (FIN) AF: 0.946 AC: 5641 AN: 5962

Middle Eastern (MID) AF: 0.893 AC: 192 AN: 215

European-Non Finnish (NFE) AF: 0.880 AC: 46682 AN: 53051

Other (OTH) AF: 0.901 AC: 1374 AN: 1525

Alfa AF: 0.890 Hom.: 79634

Bravo AF: 0.902

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Oculofaciocardiodental syndrome (3)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.043
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5917933; hg19: chrX-39933339; COSMIC: COSV60699640; COSMIC: COSV60699640;