rs142686469

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001123385.2(BCOR):c.3847+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,203,517 control chromosomes in the GnomAD database, including 8 homozygotes. There are 272 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., 140 hem., cov: 23)

Exomes 𝑓: 0.00052 ( 5 hom. 132 hem. )

Consequence

BCOR
NM_001123385.2 splice_region, intron

Scores

Splicing: ADA: 0.00002456

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.99

Publications

1 publications found

Variant links:

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

BCOR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-40063601-C-G is Benign according to our data. Variant chrX-40063601-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00515 (580/112700) while in subpopulation AFR AF = 0.0177 (547/30986). AF 95% confidence interval is 0.0164. There are 3 homozygotes in GnomAd4. There are 140 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCOR	NM_001123385.2 link	c.3847+7G>C		splice_region_variant, intron_variant	Intron 8 of 14	ENST00000378444.9	NP_001116857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCOR	ENST00000378444.9 link	c.3847+7G>C		splice_region_variant, intron_variant	Intron 8 of 14	1	NM_001123385.2	ENSP00000367705.4

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

580

AN:

112648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

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:

0.0000375

Gnomad OTH

AF:

0.00459

GnomAD2 exomes

AF:

0.00143

AC:

261

AN:

182147

AF XY:

0.000855

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000613

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000524

AC:

572

AN:

1090817

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

132

AN XY:

356689

show subpopulations

African (AFR)

AF:

0.0179

AC:

471

AN:

26273

American (AMR)

AF:

0.00119

AC:

AN:

35172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19323

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.00

AC:

AN:

53870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40174

Middle Eastern (MID)

AF:

0.000485

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

835828

Other (OTH)

AF:

0.00105

AC:

AN:

45872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00515

AC:

580

AN:

112700

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

140

AN XY:

34856

show subpopulations

African (AFR)

AF:

0.0177

AC:

547

AN:

30986

American (AMR)

AF:

0.00223

AC:

AN:

10775

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3583

South Asian (SAS)

AF:

0.00

AC:

AN:

2745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53270

Other (OTH)

AF:

0.00453

AC:

AN:

1545

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.00609

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 14, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculofaciocardiodental syndrome

Benign:1

Dec 05, 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

-0.92

CADD

Benign

0.0070

(source)

DANN

Benign

0.48

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.010

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over