Genetic Variant NM_001379451.1:c.200G>C (chrX-130012972-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001379451.1(BCORL1):c.200G>C(p.Ser67Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,196,931 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000074 ( 0 hom. 2 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.71

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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14214742).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.200G>C	p.Ser67Thr	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.200G>C	p.Ser67Thr	missense_variant	Exon 4 of 14	1	NM_001379451.1	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11 link	c.200G>C	p.Ser67Thr	missense_variant	Exon 4 of 13	5		ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000488135.6 link	n.*218G>C		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4
BCORL1	ENST00000488135.6 link	n.*218G>C		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

AF:

0.00000883

AC:

AN:

113244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35372

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000376

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000587

AC:

AN:

170273

Hom.:

AF XY:

0.00

AC XY:

AN XY:

57945

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000157

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000738

AC:

AN:

1083687

Hom.:

Cov.:

AF XY:

0.00000567

AC XY:

AN XY:

352883

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000213

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000220

GnomAD4 genome

AF:

0.00000883

AC:

AN:

113244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000376

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Shukla-Vernon syndrome

Uncertain:1

Mar 09, 2023

Gene Discovery Core-Manton Center, Boston Children's Hospital

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.055

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.043

D;D

Vest4

0.20

MutPred

0.20

Loss of glycosylation at S67 (P = 0.0295);Loss of glycosylation at S67 (P = 0.0295);

MVP

0.48

MPC

0.38

ClinPred

0.30

GERP RS

5.3

gMVP

0.079

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