3-187729443-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001706.5(BCL6):​c.962C>T​(p.Ala321Val) variant causes a missense change. The variant allele was found at a frequency of 0.000217 in 1,609,986 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 not provided (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

6
13

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.13
Variant links:
Genes affected
BCL6 (HGNC:1001): (BCL6 transcription repressor) The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1215646).
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCL6NM_001706.5 linkuse as main transcriptc.962C>T p.Ala321Val missense_variant 5/10 ENST00000406870.7 NP_001697.2
LOC100131635NR_034062.1 linkuse as main transcriptn.294-2928G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BCL6ENST00000406870.7 linkuse as main transcriptc.962C>T p.Ala321Val missense_variant 5/101 NM_001706.5 ENSP00000384371 P1P41182-1
ENST00000449623.5 linkuse as main transcriptn.347-4081G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000846
AC:
21
AN:
248326
Hom.:
0
AF XY:
0.000104
AC XY:
14
AN XY:
134120
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000291
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:
0.000151
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000230
AC:
335
AN:
1457882
Hom.:
0
Cov.:
34
AF XY:
0.000219
AC XY:
159
AN XY:
724834
show subpopulations
Gnomad4 AFR exome
AF:
0.0000900
Gnomad4 AMR exome
AF:
0.0000225
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:
0.000291
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.000106
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
.;T;T;.
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;.;D;.
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N;N;N
MutationTaster
Benign
0.92
D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.3
.;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.15
.;T;T;T
Sift4G
Benign
0.46
T;T;T;T
Polyphen
0.52
.;P;P;.
Vest4
0.23
MVP
0.30
MPC
0.20
ClinPred
0.054
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.24

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: rs377059215; hg19: chr3-187447231; API