chr1-147611852-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004326.4(BCL9):​c.16C>A​(p.Pro6Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BCL9
NM_004326.4 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31399214).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCL9NM_004326.4 linkc.16C>A p.Pro6Thr missense_variant Exon 4 of 10 ENST00000234739.8 NP_004317.2 O00512A0A024QYY4Q1JQ81
LOC128071544NM_001414892.1 linkc.*56C>A downstream_gene_variant NP_001401821.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCL9ENST00000234739.8 linkc.16C>A p.Pro6Thr missense_variant Exon 4 of 10 1 NM_004326.4 ENSP00000234739.3 O00512
ENSG00000288626ENST00000675347.1 linkc.*56C>A downstream_gene_variant ENSP00000502794.1 A0A6Q8PHS2

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000399
AC:
10
AN:
250820
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.0000619
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.16C>A (p.P6T) alteration is located in exon 4 (coding exon 1) of the BCL9 gene. This alteration results from a C to A substitution at nucleotide position 16, causing the proline (P) at amino acid position 6 to be replaced by a threonine (T). 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
0.16
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.072
T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.3
L
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.16
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.023
D
Polyphen
1.0
D
Vest4
0.48
MutPred
0.26
Gain of phosphorylation at P6 (P = 0.0162);
MVP
0.30
MPC
0.41
ClinPred
0.45
T
GERP RS
5.6
Varity_R
0.49
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs782589783; hg19: chr1-147083651; API