X-40052187-C-T

Variant names:

• chrX-40052187-C-T
• rs375139386
• NM_001123385.2:c.5190G>A

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.5190G>A​(p.Thr1730Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,209,128 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 76 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 0.00034 (0 hom., 8 hem., cov: 24)
  • Exomes 𝑓: 0.00021 (0 hom. 68 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.88
• 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• 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=-0.89).
• BP6: Variant X-40052187-C-T is Benign according to our data. Variant chrX-40052187-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 696103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000339 (38/112106) while in subpopulation AFR AF = 0.000551 (17/30852). AF 95% confidence interval is 0.000351. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 8 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.5190G>A	p.Thr1730Thr	synonymous	Exon 15 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.5190G>A	p.Thr1730Thr	synonymous	Exon 15 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.5136G>A	p.Thr1712Thr	synonymous	Exon 14 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.5190G>A	p.Thr1730Thr	synonymous	Exon 15 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.5088G>A	p.Thr1696Thr	synonymous	Exon 15 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.5034G>A	p.Thr1678Thr	synonymous	Exon 14 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.000339 AC: 38 AN: 112106 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000319

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.000178 AC: 32 AN: 179418 AF XY: 0.000234

Gnomad AFR exome AF: 0.00108

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.000270

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000214 AC: 235 AN: 1097022 Hom.: 0 Cov.: 30 AF XY: 0.000188 AC XY: 68 AN XY: 362458

African (AFR) AF: 0.000455 AC: 12 AN: 26391

American (AMR) AF: 0.0000285 AC: 1 AN: 35110

Ashkenazi Jewish (ASJ) AF: 0.000207 AC: 4 AN: 19365

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30194

South Asian (SAS) AF: 0.0000372 AC: 2 AN: 53827

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40477

Middle Eastern (MID) AF: 0.000968 AC: 4 AN: 4134

European-Non Finnish (NFE) AF: 0.000239 AC: 201 AN: 841461

Other (OTH) AF: 0.000174 AC: 8 AN: 46063

GnomAD4 genome AF: 0.000339 AC: 38 AN: 112106 Hom.: 0 Cov.: 24 AF XY: 0.000233 AC XY: 8 AN XY: 34272

African (AFR) AF: 0.000551 AC: 17 AN: 30852

American (AMR) AF: 0.00 AC: 0 AN: 10551

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 3 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3587

South Asian (SAS) AF: 0.00 AC: 0 AN: 2720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000319 AC: 17 AN: 53266

Other (OTH) AF: 0.000664 AC: 1 AN: 1505

Alfa AF: 0.000182 Hom.: 2

Bravo AF: 0.000393

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.035
DANN	Benign	0.30
PhyloP100		-1.9
Mutation Taster		=99/1	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: rs375139386; hg19: chrX-39911440; COSMIC: COSV60717577;