chr3-187729200-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001706.5(BCL6):​c.1205G>A​(p.Arg402His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,592,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

6
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009298384).
BP6
Variant 3-187729200-C-T is Benign according to our data. Variant chr3-187729200-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 729094.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 160 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCL6NM_001706.5 linkuse as main transcriptc.1205G>A p.Arg402His missense_variant 5/10 ENST00000406870.7 NP_001697.2
LOC100131635NR_034062.1 linkuse as main transcriptn.294-3171C>T 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.1205G>A p.Arg402His missense_variant 5/101 NM_001706.5 ENSP00000384371 P1P41182-1
ENST00000449623.5 linkuse as main transcriptn.347-4324C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00106
AC:
160
AN:
151280
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00331
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
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:
0.0000148
Gnomad OTH
AF:
0.000963
GnomAD3 exomes
AF:
0.000322
AC:
80
AN:
248276
Hom.:
1
AF XY:
0.000216
AC XY:
29
AN XY:
134150
show subpopulations
Gnomad AFR exome
AF:
0.00317
Gnomad AMR exome
AF:
0.000443
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:
0.0000621
Gnomad OTH exome
AF:
0.00117
GnomAD4 exome
AF:
0.000117
AC:
168
AN:
1441522
Hom.:
1
Cov.:
31
AF XY:
0.000107
AC XY:
77
AN XY:
716496
show subpopulations
Gnomad4 AFR exome
AF:
0.00295
Gnomad4 AMR exome
AF:
0.000370
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000909
Gnomad4 OTH exome
AF:
0.000253
GnomAD4 genome
AF:
0.00106
AC:
160
AN:
151400
Hom.:
0
Cov.:
32
AF XY:
0.000973
AC XY:
72
AN XY:
74024
show subpopulations
Gnomad4 AFR
AF:
0.00330
Gnomad4 AMR
AF:
0.00138
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.000953
Alfa
AF:
0.000200
Hom.:
1
Bravo
AF:
0.000990
ESP6500AA
AF:
0.00340
AC:
15
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000346
AC:
42
EpiCase
AF:
0.0000555
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
.;T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.82
T;.;T;.
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.0093
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N;N;N
MutationTaster
Benign
0.91
N;N;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.59
.;N;N;N
REVEL
Benign
0.073
Sift
Benign
0.17
.;T;T;T
Sift4G
Benign
0.094
T;T;T;T
Polyphen
0.95
.;P;P;.
Vest4
0.20
MVP
0.41
MPC
0.22
ClinPred
0.027
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.040
gMVP
0.27

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: rs139744042; hg19: chr3-187446988; API