X-40072655-C-A

Variant names:

• chrX-40072655-C-A
• rs3810693
• NM_001123385.2:c.2691G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001123385.2(BCOR):​c.2691G>T​(p.Ser897Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,210,445 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 85 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S897S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., 19 hem., cov: 24)
  • Exomes 𝑓: 0.00018 (0 hom. 66 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51
• Publications: 4 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-40072655-C-A is Benign according to our data. Variant chrX-40072655-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2182685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000303 (34/112239) while in subpopulation SAS AF = 0.000367 (1/2723). AF 95% confidence interval is 0.0000744. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 19 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.2691G>T	p.Ser897Ser	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.2691G>T	p.Ser897Ser	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.2691G>T	p.Ser897Ser	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.2691G>T	p.Ser897Ser	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.2691G>T	p.Ser897Ser	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.2691G>T	p.Ser897Ser	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.000303 AC: 34 AN: 112184 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.00394

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.000662

GnomAD2 exomes AF: 0.000376 AC: 69 AN: 183433 AF XY: 0.000354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00294

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000182 AC: 200 AN: 1098206 Hom.: 0 Cov.: 30 AF XY: 0.000182 AC XY: 66 AN XY: 363566

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.000185 AC: 10 AN: 54147

European-Finnish (FIN) AF: 0.00264 AC: 107 AN: 40507

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000891 AC: 75 AN: 842125

Other (OTH) AF: 0.000174 AC: 8 AN: 46097

GnomAD4 genome AF: 0.000303 AC: 34 AN: 112239 Hom.: 0 Cov.: 24 AF XY: 0.000552 AC XY: 19 AN XY: 34415

African (AFR) AF: 0.00 AC: 0 AN: 30904

American (AMR) AF: 0.00 AC: 0 AN: 10665

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.000367 AC: 1 AN: 2723

European-Finnish (FIN) AF: 0.00394 AC: 24 AN: 6092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53210

Other (OTH) AF: 0.000654 AC: 1 AN: 1529

Alfa AF: 0.0000364 Hom.: 1

Bravo AF: 0.0000491

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.037
DANN	Benign	0.50
PhyloP100		-3.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	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: rs3810693; hg19: chrX-39931908;