Genetic Variant BCORL1:p.Arg72Trp (chrX-130012986-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001379451.1(BCORL1):c.214C>T(p.Arg72Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000512 in 1,201,146 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 174 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 0.00035 ( 0 hom., 11 hem., cov: 24)

Exomes 𝑓: 0.00053 ( 0 hom. 163 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.58

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14974695).

BP6

Variant X-130012986-C-T is Benign according to our data. Variant chrX-130012986-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661409.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1 link	c.214C>T	p.Arg72Trp	missense_variant	Exon 4 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCORL1	ENST00000540052.6 link	c.214C>T	p.Arg72Trp	missense_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11 link	c.214C>T	p.Arg72Trp	missense_variant	Exon 4 of 13	5		ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000488135.6 link	n.*232C>T		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4
BCORL1	ENST00000488135.6 link	n.*232C>T		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

AF:

0.000354

AC:

AN:

112847

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

AN XY:

35015

show subpopulations

Gnomad AFR

AF:

0.000354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.000507

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

173006

Hom.:

AF XY:

0.000198

AC XY:

AN XY:

60594

show subpopulations

Gnomad AFR exome

AF:

0.0000807

Gnomad AMR exome

AF:

0.000189

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:

0.000351

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000528

AC:

575

AN:

1088299

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

163

AN XY:

355699

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

Gnomad4 AMR exome

AF:

0.000144

Gnomad4 ASJ exome

AF:

0.0000527

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000354

AC:

AN:

112847

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

AN XY:

35015

show subpopulations

Gnomad4 AFR

AF:

0.000354

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000507

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000488

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000746

AC:

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BCORL1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.069

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.77

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.022

D;D

Vest4

0.46

MVP

0.56

MPC

0.43

ClinPred

0.11

GERP RS

5.3

gMVP

0.090

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