rs778701486

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4BP6_ModerateBS2_Supporting

The NM_001379451.1(BCORL1):c.62G>A(p.Arg21His) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,209,942 control chromosomes in the GnomAD database, including 1 homozygotes. There are 49 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 0.00016 ( 1 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 0 hom. 43 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:2B:1

Conservation

PhyloP100: 7.11

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35522416).

BP6

Variant X-130005293-G-A is Benign according to our data. Variant chrX-130005293-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1299882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCORL1	NM_001379451.1 link	c.62G>A	p.Arg21His	missense_variant	Exon 2 of 14	ENST00000540052.6	NP_001366380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCORL1	ENST00000540052.6 link	c.62G>A	p.Arg21His	missense_variant	Exon 2 of 14	1	NM_001379451.1	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11 link	c.62G>A	p.Arg21His	missense_variant	Exon 2 of 13	5		ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000607874.1 link	c.62G>A	p.Arg21His	missense_variant	Exon 3 of 3	3		ENSP00000484149.1	A0A087X1F0
BCORL1	ENST00000488135.6 link	n.62G>A		non_coding_transcript_exon_variant	Exon 3 of 6	3		ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

112180

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34322

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.000244

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000819

AC:

AN:

183246

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67704

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000979

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

142

AN:

1097762

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

363138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000160

AC:

AN:

112180

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34322

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000244

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BCORL1: BS2 -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;.;.

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Uncertain

-0.062

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.4

.;N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.0010

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.58, 0.50

MVP

0.91

MPC

0.52

ClinPred

0.14

GERP RS

4.7

gMVP

0.45

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