Menu
GeneBe

1-147619684-T-G

Variant summary

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

The NM_004326.4(BCL9):c.1529T>G(p.Val510Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V510A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

BCL9
NM_004326.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89
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]

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=0.14178583).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL9NM_004326.4 linkuse as main transcriptc.1529T>G p.Val510Gly missense_variant 8/10 ENST00000234739.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL9ENST00000234739.8 linkuse as main transcriptc.1529T>G p.Val510Gly missense_variant 8/101 NM_004326.4 P2
BCL9ENST00000683836.1 linkuse as main transcriptc.1529T>G p.Val510Gly missense_variant 8/10
BCL9ENST00000684121.1 linkuse as main transcriptc.1307T>G p.Val436Gly missense_variant 6/8 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000800
AC:
2
AN:
249912
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461810
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727208
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:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsMay 27, 2022The c.1529T>G (p.V510G) alteration is located in exon 8 (coding exon 5) of the BCL9 gene. This alteration results from a T to G substitution at nucleotide position 1529, causing the valine (V) at amino acid position 510 to be replaced by a glycine (G). 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
0.22
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.29
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.027
Eigen_PC
Benign
0.18
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.19
Sift
Benign
0.11
T
Sift4G
Uncertain
0.055
T
Polyphen
0.0010
B
Vest4
0.30
MutPred
0.22
Loss of stability (P = 0.0235);
MVP
0.15
MPC
0.11
ClinPred
0.24
T
GERP RS
5.5
Varity_R
0.17
gMVP
0.44

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.

Other links and lift over

dbSNP: rs1054557337; hg19: chr1-147091490; API