Genetic Variant BCORL1:p.Asn104Lys (chrX-130013084-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001379451.1(BCORL1):c.312C>A(p.Asn104Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N104H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

BCORL1
NM_001379451.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.960

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08535996).

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.312C>A	p.Asn104Lys	missense	Exon 4 of 14	NP_001366380.1	Q5H9F3-3
BCORL1	NM_001184772.3		c.312C>A	p.Asn104Lys	missense	Exon 5 of 15	NP_001171701.1	Q5H9F3-3
BCORL1	NM_001379450.1		c.312C>A	p.Asn104Lys	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.312C>A	p.Asn104Lys	missense	Exon 4 of 14	ENSP00000437775.2	Q5H9F3-3
BCORL1	ENST00000218147.11	TSL:5	c.312C>A	p.Asn104Lys	missense	Exon 4 of 13	ENSP00000218147.7	Q5H9F3-1
BCORL1	ENST00000488135.6	TSL:3	n.*330C>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000476643.1	V9GYD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096791

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362287

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26381

American (AMR)

AF:

0.00

AC:

AN:

35177

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19372

East Asian (EAS)

AF:

0.00

AC:

AN:

30143

South Asian (SAS)

AF:

0.00

AC:

AN:

54121

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

840960

Other (OTH)

AF:

0.00

AC:

AN:

45998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0040

(source)

DANN

Benign

0.95

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.013

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.99

PhyloP100

-0.96

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.35

REVEL

Benign

0.019

Sift

Benign

0.23

Sift4G

Benign

0.45

Vest4

0.099

MutPred

0.31

Gain of ubiquitination at N104 (P = 0.0016)

MVP

0.17

MPC

0.48

ClinPred

0.24

GERP RS

-2.4

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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