Variant 11-118898520-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001378213.1(BCL9L):c.4395G>C(p.Gln1465His) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,600,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

BCL9L
NM_001378213.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

BCL9L (HGNC:23688): (BCL9 like) Enables beta-catenin binding activity. Involved in several processes, including negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of epithelial to mesenchymal transition; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

BCL9L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9L	NM_001378213.1 link	c.4395G>C	p.Gln1465His	missense_variant	10/10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BCL9L	ENST00000683865.1 link	c.4395G>C	p.Gln1465His	missense_variant	10/10		NM_001378213.1	ENSP00000507778.1	Q86UU0-1
BCL9L	ENST00000334801.7 link	c.4395G>C	p.Gln1465His	missense_variant	8/8	1		ENSP00000335320.3	Q86UU0-1
BCL9L	ENST00000526143.2 link	c.4284G>C	p.Gln1428His	missense_variant	8/8	5		ENSP00000482938.1	A0A087WZX0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1447880

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

717958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.4395G>C (p.Q1465H) alteration is located in exon 8 (coding exon 8) of the BCL9L gene. This alteration results from a G to C substitution at nucleotide position 4395, causing the glutamine (Q) at amino acid position 1465 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.99

D;.

Vest4

0.60

MutPred

0.20

Loss of glycosylation at P1462 (P = 0.174);.;

MVP

0.54

MPC

0.75

ClinPred

0.97

GERP RS

3.7

Varity_R

0.53

gMVP

0.28

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