rs17145653

Variant names:

• chrX-40073696-G-A
• rs17145653
• NM_001123385.2:c.1650C>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.1650C>T​(p.Thr550Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,211,722 control chromosomes in the GnomAD database, including 37 homozygotes. There are 3,393 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (5 hom., 263 hem., cov: 25)
  • Exomes 𝑓: 0.0089 (32 hom. 3130 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.28
• Publications: 2 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=-0.94).
• BP6: Variant X-40073696-G-A is Benign according to our data. Variant chrX-40073696-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.28 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00787 (894/113567) while in subpopulation NFE AF = 0.0117 (623/53427). AF 95% confidence interval is 0.0109. There are 5 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.1650C>T	p.Thr550Thr	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1650C>T	p.Thr550Thr	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.1650C>T	p.Thr550Thr	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.1650C>T	p.Thr550Thr	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1650C>T	p.Thr550Thr	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1650C>T	p.Thr550Thr	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.00788 AC: 894 AN: 113514 Hom.: 5 Cov.: 25

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.00597

Gnomad ASJ AF: 0.000376

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000353

Gnomad FIN AF: 0.000474

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00777

GnomAD2 exomes AF: 0.00551 AC: 1010 AN: 183300 AF XY: 0.00540

Gnomad AFR exome AF: 0.00304

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.000216

Gnomad FIN exome AF: 0.000816

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00886 AC: 9731 AN: 1098155 Hom.: 32 Cov.: 33 AF XY: 0.00861 AC XY: 3130 AN XY: 363515

African (AFR) AF: 0.00280 AC: 74 AN: 26401

American (AMR) AF: 0.00440 AC: 155 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.000722 AC: 14 AN: 19386

East Asian (EAS) AF: 0.000132 AC: 4 AN: 30203

South Asian (SAS) AF: 0.000332 AC: 18 AN: 54148

European-Finnish (FIN) AF: 0.00131 AC: 53 AN: 40479

Middle Eastern (MID) AF: 0.00242 AC: 10 AN: 4136

European-Non Finnish (NFE) AF: 0.0107 AC: 9026 AN: 842103

Other (OTH) AF: 0.00818 AC: 377 AN: 46095

GnomAD4 genome AF: 0.00787 AC: 894 AN: 113567 Hom.: 5 Cov.: 25 AF XY: 0.00736 AC XY: 263 AN XY: 35711

African (AFR) AF: 0.00316 AC: 99 AN: 31354

American (AMR) AF: 0.00596 AC: 65 AN: 10901

Ashkenazi Jewish (ASJ) AF: 0.000376 AC: 1 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3606

South Asian (SAS) AF: 0.000354 AC: 1 AN: 2826

European-Finnish (FIN) AF: 0.000474 AC: 3 AN: 6330

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 218

European-Non Finnish (NFE) AF: 0.0117 AC: 623 AN: 53427

Other (OTH) AF: 0.00767 AC: 12 AN: 1564

Alfa AF: 0.00701 Hom.: 58

Bravo AF: 0.00782

EpiCase AF: 0.0123

EpiControl AF: 0.00883

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.56
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17145653; hg19: chrX-39932949; COSMIC: COSV60705781; COSMIC: COSV60705781;