Genetic Variant NM_001706.5:c.1217G>C (chr3-187729188-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001706.5(BCL6):c.1217G>C(p.Arg406Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,574,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

BCL6
NM_001706.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL6	NM_001706.5	MANE Select	c.1217G>C	p.Arg406Pro	missense	Exon 5 of 10	NP_001697.2
BCL6	NM_001130845.2		c.1217G>C	p.Arg406Pro	missense	Exon 5 of 10	NP_001124317.1	P41182-1
BCL6	NM_001134738.2		c.1217G>C	p.Arg406Pro	missense	Exon 5 of 9	NP_001128210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL6	ENST00000406870.7	TSL:1 MANE Select	c.1217G>C	p.Arg406Pro	missense	Exon 5 of 10	ENSP00000384371.2	P41182-1
BCL6	ENST00000232014.8	TSL:1	c.1217G>C	p.Arg406Pro	missense	Exon 5 of 10	ENSP00000232014.4	P41182-1
BCL6	ENST00000450123.6	TSL:1	c.1217G>C	p.Arg406Pro	missense	Exon 4 of 8	ENSP00000413122.2	P41182-2

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

149674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000493

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

245638

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000386

AC:

AN:

1424956

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

707732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32556

American (AMR)

AF:

0.00

AC:

AN:

42468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

38102

South Asian (SAS)

AF:

0.00

AC:

AN:

79720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

1090930

Other (OTH)

AF:

0.0000342

AC:

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000200

AC:

AN:

149674

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73126

show subpopulations

African (AFR)

AF:

0.0000493

AC:

AN:

40546

American (AMR)

AF:

0.00

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5018

South Asian (SAS)

AF:

0.00

AC:

AN:

4730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67106

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

2.3

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

REVEL

Benign

0.11

Sift

Uncertain

0.024

Sift4G

Benign

0.19

Polyphen

0.81

Vest4

0.55

MVP

0.48

MPC

0.44

ClinPred

0.38

GERP RS

5.6

Varity_R

0.26

gMVP

0.31

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over