Variant rs398123004 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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. 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCORL1	NM_001379451.1 linkuse as main transcript	c.2459A>G	p.Asn820Ser	missense_variant	4/14	ENST00000540052.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCORL1	ENST00000540052.6 linkuse as main transcript	c.2459A>G	p.Asn820Ser	missense_variant	4/14	1	NM_001379451.1	P1	Q5H9F3-3
BCORL1	ENST00000441294.1 linkuse as main transcript	c.767A>G	p.Asn256Ser	missense_variant	1/4	1
BCORL1	ENST00000218147.11 linkuse as main transcript	c.2459A>G	p.Asn820Ser	missense_variant	4/13	5			Q5H9F3-1

Frequencies

GnomAD3 genomes

AF:

0.0000887

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34901

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

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182503

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67583

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 SAS 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

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000887

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34901

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Shukla-Vernon syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 25, 2019

- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

1.0

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.052

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.71

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.11

T;T;T

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over