dbSNP rs751650335: BCOR:p.Pro326Pro (chrX-40074368-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001123385.2(BCOR):c.978G>A(p.Pro326Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000086 in 1,209,727 control chromosomes in the GnomAD database, including 1 homozygotes. There are 29 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 0.00048 ( 0 hom., 18 hem., cov: 24)

Exomes 𝑓: 0.000046 ( 1 hom. 11 hem. )

Consequence

BCOR
NM_001123385.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.21

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen, Ambry Genetics
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-40074368-C-T is Benign according to our data. Variant chrX-40074368-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 257506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000479 (54/112829) while in subpopulation AMR AF = 0.00409 (44/10768). AF 95% confidence interval is 0.00313. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 18 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCOR	NM_001123385.2	MANE Select	c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 15	NP_001116857.1	Q6W2J9-1
BCOR	NM_001437510.1		c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 15	NP_001424439.1
BCOR	NM_001438207.1		c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 14	NP_001425136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCOR	ENST00000378444.9	TSL:1 MANE Select	c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 15	ENSP00000367705.4	Q6W2J9-1
BCOR	ENST00000397354.7	TSL:1	c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 15	ENSP00000380512.3	Q6W2J9-2
BCOR	ENST00000378455.8	TSL:1	c.978G>A	p.Pro326Pro	synonymous	Exon 4 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes

AF:

0.000479

AC:

AN:

112777

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00409

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:

0.000656

GnomAD2 exomes

AF:

0.0000392

AC:

AN:

178360

AF XY:

0.0000313

show subpopulations

Gnomad AFR exome

AF:

0.0000786

Gnomad AMR exome

AF:

0.0000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000252

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.0000456

AC:

AN:

1096898

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

362386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26385

American (AMR)

AF:

0.000569

AC:

AN:

35126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19354

East Asian (EAS)

AF:

0.00

AC:

AN:

30167

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53895

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40183

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

841617

Other (OTH)

AF:

0.000326

AC:

AN:

46037

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000479

AC:

AN:

112829

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

AN XY:

34987

show subpopulations

African (AFR)

AF:

0.000225

AC:

AN:

31119

American (AMR)

AF:

0.00409

AC:

AN:

10768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3564

South Asian (SAS)

AF:

0.00

AC:

AN:

2767

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53274

Other (OTH)

AF:

0.000648

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

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:

0.00

Hom.:

Bravo

AF:

0.000907

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.052

(source)

DANN

Benign

0.64

PhyloP100

-4.2

Mutation Taster

=99/1

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over