Variant 1-147619060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004326.4(BCL9):c.905G>A(p.Gly302Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,612,716 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

BCL9
NM_004326.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.44

Variant links:

Genes affected

BCL9 (HGNC:1008): (BCL9 transcription coactivator) BCL9 is associated with B-cell acute lymphoblastic leukemia. It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. Its function is unknown. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies. [provided by RefSeq, Jul 2008]

BCL9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034623146).

BP6

Variant 1-147619060-G-A is Benign according to our data. Variant chr1-147619060-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 708511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL9	NM_004326.4 linkuse as main transcript	c.905G>A	p.Gly302Asp	missense_variant	8/10	ENST00000234739.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BCL9	ENST00000234739.8 linkuse as main transcript	c.905G>A	p.Gly302Asp	missense_variant	8/10	1	NM_004326.4	P2
BCL9	ENST00000683836.1 linkuse as main transcript	c.905G>A	p.Gly302Asp	missense_variant	8/10
BCL9	ENST00000684121.1 linkuse as main transcript	c.683G>A	p.Gly228Asp	missense_variant	6/8			A1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00174

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00110

AC:

275

AN:

249326

Hom.:

AF XY:

0.00123

AC XY:

166

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000889

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00126

AC:

1837

AN:

1460524

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

961

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00256

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000941

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152192

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00174

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00261

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00110

AC:

134

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

BCL9-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.066

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

REVEL

Benign

0.21

Sift

Benign

0.14

Sift4G

Benign

0.20

Polyphen

0.88

Vest4

0.44

MVP

0.40

MPC

0.20

ClinPred

0.027

GERP RS

3.7

Varity_R

0.17

gMVP

0.42

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