rs61752081

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001706.5(BCL6):c.492G>T(p.Glu164Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,614,044 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.023 ( 39 hom., cov: 32)

Exomes 𝑓: 0.030 ( 722 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.13

Publications

19 publications found

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:

ENSG00000228804 (HGNC:):

ENSG00000228804 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003096044).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0232 (3540/152278) while in subpopulation NFE AF = 0.0331 (2253/68024). AF 95% confidence interval is 0.032. There are 39 homozygotes in GnomAd4. There are 1644 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 3540 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5 link	c.492G>T	p.Glu164Asp	missense_variant	Exon 5 of 10	ENST00000406870.7	NP_001697.2	P41182-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7 link	c.492G>T	p.Glu164Asp	missense_variant	Exon 5 of 10	1	NM_001706.5	ENSP00000384371.2		P41182-1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3542

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0453

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0331

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0221

AC:

5552

AN:

251196

AF XY:

0.0223

show subpopulations

Gnomad AFR exome

AF:

0.00665

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0295

AC:

43138

AN:

1461766

Hom.:

722

Cov.:

AF XY:

0.0289

AC XY:

21002

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.00568

AC:

190

AN:

33478

American (AMR)

AF:

0.0172

AC:

767

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0488

AC:

1274

AN:

26126

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00613

AC:

529

AN:

86228

European-Finnish (FIN)

AF:

0.0251

AC:

1339

AN:

53416

Middle Eastern (MID)

AF:

0.0215

AC:

124

AN:

5766

European-Non Finnish (NFE)

AF:

0.0333

AC:

37055

AN:

1111960

Other (OTH)

AF:

0.0308

AC:

1858

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2760

5520

8279

11039

13799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1372

2744

4116

5488

6860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3540

AN:

152278

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1644

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00710

AC:

295

AN:

41550

American (AMR)

AF:

0.0270

AC:

413

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0453

AC:

157

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00601

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0245

AC:

260

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0331

AC:

2253

AN:

68024

Other (OTH)

AF:

0.0345

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0283

Hom.:

145

Bravo

AF:

0.0235

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0340

AC:

131

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0331

AC:

285

ExAC

AF:

0.0206

AC:

2504

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0338

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

T;.;T;.

MetaRNN

Benign

0.0031

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

L;L;L;L

PhyloP100

1.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.63

.;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.28

.;T;T;T

Sift4G

Benign

0.43

T;T;T;T

Polyphen

0.0070

.;B;B;.

Vest4

0.076

MutPred

0.11

Loss of glycosylation at P168 (P = 0.1164);Loss of glycosylation at P168 (P = 0.1164);Loss of glycosylation at P168 (P = 0.1164);Loss of glycosylation at P168 (P = 0.1164);

MPC

0.16

ClinPred

0.010

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.14

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over