rs5963725

Variant names:

• chrX-40052404-C-A
• rs5963725
• NM_001123385.2:c.4977-4G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-40052404-C-A
• chrX-40052404-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000378444.9(BCOR):​c.4977-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,205,271 control chromosomes in the GnomAD database, including 14,154 homozygotes. There are 70,182 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1280 hom., 4989 hem., cov: 22)
  • Exomes 𝑓: 0.18 (12874 hom. 65193 hem.)
• Consequence: BCOR ENST00000378444.9 splice_region, intron
• Scores: Splicing: ADA: 0.00003587
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.71
• Publications: 8 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: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-40052404-C-A is Benign according to our data. Variant chrX-40052404-C-A is described in ClinVar as Benign. ClinVar VariationId is 95772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378444.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.4977-4G>T		splice_region intron	N/A	NP_001116857.1
	BCOR	NM_001437510.1		c.4977-4G>T		splice_region intron	N/A	NP_001424439.1
	BCOR	NM_001438207.1		c.4923-4G>T		splice_region intron	N/A	NP_001425136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.4977-4G>T		splice_region intron	N/A	ENSP00000367705.4
	BCOR	ENST00000397354.7	TSL:1	c.4875-4G>T		splice_region intron	N/A	ENSP00000380512.3
	BCOR	ENST00000378455.8	TSL:1	c.4821-4G>T		splice_region intron	N/A	ENSP00000367716.4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 18570 AN: 110308 Hom.: 1282 Cov.: 22

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.000559

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.149 AC: 27117 AN: 181988 AF XY: 0.154

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0765

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.00108

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.181 AC: 197935 AN: 1094910 Hom.: 12874 Cov.: 31 AF XY: 0.181 AC XY: 65193 AN XY: 360718

African (AFR) AF: 0.169 AC: 4463 AN: 26343

American (AMR) AF: 0.0830 AC: 2918 AN: 35157

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3128 AN: 19367

East Asian (EAS) AF: 0.000564 AC: 17 AN: 30164

South Asian (SAS) AF: 0.192 AC: 10349 AN: 54031

European-Finnish (FIN) AF: 0.121 AC: 4918 AN: 40494

Middle Eastern (MID) AF: 0.258 AC: 1064 AN: 4128

European-Non Finnish (NFE) AF: 0.194 AC: 162800 AN: 839272

Other (OTH) AF: 0.180 AC: 8278 AN: 45954

GnomAD4 genome AF: 0.168 AC: 18561 AN: 110361 Hom.: 1280 Cov.: 22 AF XY: 0.153 AC XY: 4989 AN XY: 32647

African (AFR) AF: 0.171 AC: 5174 AN: 30345

American (AMR) AF: 0.130 AC: 1344 AN: 10333

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 410 AN: 2633

East Asian (EAS) AF: 0.000560 AC: 2 AN: 3569

South Asian (SAS) AF: 0.177 AC: 455 AN: 2575

European-Finnish (FIN) AF: 0.104 AC: 598 AN: 5743

Middle Eastern (MID) AF: 0.203 AC: 44 AN: 217

European-Non Finnish (NFE) AF: 0.192 AC: 10124 AN: 52782

Other (OTH) AF: 0.150 AC: 225 AN: 1499

Alfa AF: 0.185 Hom.: 2312

Bravo AF: 0.169

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-2.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
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: rs5963725; hg19: chrX-39911657;