rs113588421

Variant names:

• chrX-40052340-T-A
• rs113588421
• NM_001123385.2:c.5037A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-40052340-T-A
• chrX-40052340-T-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001123385.2(BCOR):​c.5037A>T​(p.Ile1679Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,210,107 control chromosomes in the GnomAD database, including 3 homozygotes. There are 60 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., 20 hem., cov: 23)
  • Exomes 𝑓: 0.00012 (3 hom. 40 hem.)
• Consequence: BCOR NM_001123385.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-40052340-T-A is Benign according to our data. Variant chrX-40052340-T-A is described in ClinVar as Benign. ClinVar VariationId is 465162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000491 (55/112084) while in subpopulation AFR AF = 0.00149 (46/30898). AF 95% confidence interval is 0.00115. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 20 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2	c.5037A>T	p.Ile1679Ile	synonymous_variant	Exon 15 of 15	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9	c.5037A>T	p.Ile1679Ile	synonymous_variant	Exon 15 of 15	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes AF: 0.000446 AC: 50 AN: 112031 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000751

Gnomad OTH AF: 0.000665

GnomAD2 exomes AF: 0.000131 AC: 24 AN: 183469 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.000182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 127 AN: 1098023 Hom.: 3 Cov.: 30 AF XY: 0.000110 AC XY: 40 AN XY: 363377

African (AFR) AF: 0.00223 AC: 59 AN: 26399

American (AMR) AF: 0.000256 AC: 9 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841935

Other (OTH) AF: 0.00117 AC: 54 AN: 46087

GnomAD4 genome AF: 0.000491 AC: 55 AN: 112084 Hom.: 0 Cov.: 23 AF XY: 0.000584 AC XY: 20 AN XY: 34252

African (AFR) AF: 0.00149 AC: 46 AN: 30898

American (AMR) AF: 0.000379 AC: 4 AN: 10568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53227

Other (OTH) AF: 0.000657 AC: 1 AN: 1522

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000586

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oculofaciocardiodental syndrome Benign:1

May 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		-0.018
Mutation Taster		=98/2	polymorphism

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: rs113588421; hg19: chrX-39911593;