3-187729200-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

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]

BCL6 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, BCL6

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 GnomAd at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL6	NM_001706.5 linkuse as main transcript	c.1205G>A	p.Arg402His	missense_variant	5/10	ENST00000406870.7
LOC100131635	NR_034062.1 linkuse as main transcript	n.294-3171C>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.1205G>A	p.Arg402His	missense_variant	5/10	1	NM_001706.5	P1	P41182-1
	ENST00000449623.5 linkuse as main transcript	n.347-4324C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

160

AN:

151280

Hom.:

Cov.:

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:

AN:

248276

Hom.:

AF XY:

0.000216

AC XY:

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.:

Cov.:

AF XY:

0.000107

AC XY:

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.:

Cov.:

AF XY:

0.000973

AC XY:

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.:

Bravo

AF:

0.000990

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

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 submitter

clinical testing

Invitae

Dec 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;.;T;.

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0093

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

0.91

N;N;N

PrimateAI

Uncertain

0.53

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

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.

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