Variant 11-118898510-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378213.1(BCL9L):c.4405A>C(p.Met1469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BCL9L
NM_001378213.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2341047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9L	NM_001378213.1 linkuse as main transcript	c.4405A>C	p.Met1469Leu	missense_variant	10/10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL9L	ENST00000683865.1 linkuse as main transcript	c.4405A>C	p.Met1469Leu	missense_variant	10/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.4405A>C	p.Met1469Leu	missense_variant	8/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.4294A>C	p.Met1432Leu	missense_variant	8/8	5		ENSP00000482938	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1449214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718652

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 03, 2022

The c.4405A>C (p.M1469L) alteration is located in exon 8 (coding exon 8) of the BCL9L gene. This alteration results from a A to C substitution at nucleotide position 4405, causing the methionine (M) at amino acid position 1469 to be replaced by a leucine (L). 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

Benign

0.18

BayesDel_addAF

Benign

0.0046

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.89

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.28

Sift

Benign

0.084

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.0030

B;.

Vest4

0.48

MutPred

0.27

Loss of catalytic residue at M1469 (P = 0.0325);.;

MVP

0.70

MPC

0.19

ClinPred

0.51

GERP RS

3.7

Varity_R

0.37

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over