rs144606152

Variant names:

• chrX-40073555-G-A
• rs144606152
• NM_001123385.2:c.1791C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-40073555-G-A
• chrX-40073555-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001123385.2(BCOR):​c.1791C>T​(p.His597His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,211,156 control chromosomes in the GnomAD database, including 977 homozygotes. There are 16,949 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (58 hom., 1026 hem., cov: 25)
  • Exomes 𝑓: 0.045 (919 hom. 15923 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0260
• Publications: 5 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=-0.73).
• BP6: Variant X-40073555-G-A is Benign according to our data. Variant chrX-40073555-G-A is described in ClinVar as Benign. ClinVar VariationId is 95767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.026 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

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.1791C>T	p.His597His	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.1791C>T	p.His597His	synonymous	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.1791C>T	p.His597His	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.1791C>T	p.His597His	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.1791C>T	p.His597His	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.1791C>T	p.His597His	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 3598 AN: 113134 Hom.: 58 Cov.: 25

Gnomad AFR AF: 0.00686

Gnomad AMI AF: 0.0131

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0621

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.0379

GnomAD2 exomes AF: 0.0345 AC: 6314 AN: 183017 AF XY: 0.0349

Gnomad AFR exome AF: 0.00623

Gnomad AMR exome AF: 0.0188

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.0000721

Gnomad FIN exome AF: 0.0372

Gnomad NFE exome AF: 0.0517

Gnomad OTH exome AF: 0.0431

GnomAD4 exome AF: 0.0448 AC: 49170 AN: 1097967 Hom.: 919 Cov.: 31 AF XY: 0.0438 AC XY: 15923 AN XY: 363357

African (AFR) AF: 0.00633 AC: 167 AN: 26402

American (AMR) AF: 0.0187 AC: 660 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.0607 AC: 1176 AN: 19386

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30206

South Asian (SAS) AF: 0.0140 AC: 760 AN: 54148

European-Finnish (FIN) AF: 0.0387 AC: 1559 AN: 40262

Middle Eastern (MID) AF: 0.0607 AC: 251 AN: 4135

European-Non Finnish (NFE) AF: 0.0506 AC: 42622 AN: 842124

Other (OTH) AF: 0.0428 AC: 1973 AN: 46097

GnomAD4 genome AF: 0.0318 AC: 3594 AN: 113189 Hom.: 58 Cov.: 25 AF XY: 0.0290 AC XY: 1026 AN XY: 35335

African (AFR) AF: 0.00685 AC: 214 AN: 31263

American (AMR) AF: 0.0221 AC: 239 AN: 10833

Ashkenazi Jewish (ASJ) AF: 0.0621 AC: 165 AN: 2655

East Asian (EAS) AF: 0.000279 AC: 1 AN: 3582

South Asian (SAS) AF: 0.0122 AC: 34 AN: 2779

European-Finnish (FIN) AF: 0.0340 AC: 214 AN: 6297

Middle Eastern (MID) AF: 0.0639 AC: 14 AN: 219

European-Non Finnish (NFE) AF: 0.0496 AC: 2647 AN: 53328

Other (OTH) AF: 0.0368 AC: 57 AN: 1548

Alfa AF: 0.0454 Hom.: 373

Bravo AF: 0.0294

EpiCase AF: 0.0545

EpiControl AF: 0.0560

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	History of neurodevelopmental disorder (1)
-	-	1	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.48
DANN	Benign	0.48
PhyloP100		-0.026
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs144606152; hg19: chrX-39932808; COSMIC: COSV60705224; COSMIC: COSV60705224;