dbSNP rs398123004: BCORL1:p.Asn820Ser (chrX-130015231-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001379451.1(BCORL1):c.2459A>G(p.Asn820Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,210,772 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 4 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 5.45

Publications

3 publications found

Variant links:

Genes affected

BCORL1 (HGNC:25657): (BCL6 corepressor like 1) The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

BCORL1 Gene-Disease associations (from GenCC):

Shukla-Vernon syndrome
Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BCORL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23523194).

BS2

High AC in GnomAd4 at 10 XL,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCORL1	NM_001379451.1	MANE Select	c.2459A>G	p.Asn820Ser	missense	Exon 4 of 14	NP_001366380.1	Q5H9F3-3
BCORL1	NM_001184772.3		c.2459A>G	p.Asn820Ser	missense	Exon 5 of 15	NP_001171701.1	Q5H9F3-3
BCORL1	NM_001379450.1		c.2459A>G	p.Asn820Ser	missense	Exon 4 of 14	NP_001366379.1	Q5H9F3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCORL1	ENST00000540052.6	TSL:1 MANE Select	c.2459A>G	p.Asn820Ser	missense	Exon 4 of 14	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000441294.1	TSL:1	c.764A>G	p.Asn255Ser	missense	Exon 1 of 4	ENSP00000416520.1	H7C4B2
BCORL1	ENST00000218147.11	TSL:5	c.2459A>G	p.Asn820Ser	missense	Exon 4 of 13	ENSP00000218147.7	Q5H9F3-1

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112755

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

182503

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1098017

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363497

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

842150

Other (OTH)

AF:

0.0000217

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.0000887

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34901

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

31069

American (AMR)

AF:

0.00

AC:

AN:

10734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00

AC:

AN:

2791

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53238

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000341

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Shukla-Vernon syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.052

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.71

PhyloP100

5.4

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Vest4

0.36

MVP

0.71

MPC

1.0

ClinPred

0.49

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.20

Mutation Taster

=89/11

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over