Variant chr3-187728423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001706.5(BCL6):c.1477G>A(p.Ala493Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,610,620 control chromosomes in the GnomAD database, including 22,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4580 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18278 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.463

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]

BCL6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022749603).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL6	NM_001706.5 linkuse as main transcript	c.1477G>A	p.Ala493Thr	missense_variant	6/10	ENST00000406870.7
LOC100131635	NR_034062.1 linkuse as main transcript	n.294-3948C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL6	ENST00000406870.7 linkuse as main transcript	c.1477G>A	p.Ala493Thr	missense_variant	6/10	1	NM_001706.5	P1	P41182-1
	ENST00000449623.5 linkuse as main transcript	n.347-5101C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32238

AN:

151906

Hom.:

4570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.0967

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0740

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.143

AC:

34854

AN:

244402

Hom.:

3195

AF XY:

0.138

AC XY:

18269

AN XY:

131962

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0709

Gnomad SAS exome

AF:

0.0983

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.150

AC:

218845

AN:

1458596

Hom.:

18278

Cov.:

AF XY:

0.148

AC XY:

107306

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.0804

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.212

AC:

32277

AN:

152024

Hom.:

4580

Cov.:

AF XY:

0.206

AC XY:

15285

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.0736

Gnomad4 SAS

AF:

0.0932

Gnomad4 FIN

AF:

0.0947

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.160

Hom.:

3728

Bravo

AF:

0.226

TwinsUK

AF:

0.147

AC:

544

ALSPAC

AF:

0.159

AC:

611

ESP6500AA

AF:

0.405

AC:

1784

ESP6500EA

AF:

0.152

AC:

1308

ExAC

AF:

0.147

AC:

17864

Asia WGS

AF:

0.116

AC:

404

AN:

3478

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 provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.25

.;T;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

T;.;T;.

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.010

.;N;N;N

REVEL

Benign

0.038

Sift

Benign

0.42

.;T;T;T

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.0040

.;B;B;.

Vest4

0.098

MPC

0.17

ClinPred

0.00088

GERP RS

-0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.15

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