NM_001706.5:c.1375C>T

Variant names:

• chr3-187728525-G-A
• rs137878288
• NM_001706.5:c.1375C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001706.5(BCL6):​c.1375C>T​(p.Arg459Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,609,080 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.09
• Publications: 8 publications found

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]

ENSG00000228804 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04050383).
• BS2: High AC in GnomAd4 at 167 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.1375C>T	p.Arg459Cys	missense	Exon 6 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.1375C>T	p.Arg459Cys	missense	Exon 6 of 10	NP_001124317.1
	BCL6	NM_001134738.2		c.1375C>T	p.Arg459Cys	missense	Exon 6 of 9	NP_001128210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.1375C>T	p.Arg459Cys	missense	Exon 6 of 10	ENSP00000384371.2
	BCL6	ENST00000232014.8	TSL:1	c.1375C>T	p.Arg459Cys	missense	Exon 6 of 10	ENSP00000232014.4
	BCL6	ENST00000450123.6	TSL:1	c.1375C>T	p.Arg459Cys	missense	Exon 5 of 8	ENSP00000413122.2

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152022 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00107 AC: 263 AN: 245928 AF XY: 0.00112

Gnomad AFR exome AF: 0.000443

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000422

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00138 AC: 2005 AN: 1456940 Hom.: 1 Cov.: 32 AF XY: 0.00133 AC XY: 961 AN XY: 724814

African (AFR) AF: 0.000272 AC: 9 AN: 33074

American (AMR) AF: 0.00109 AC: 48 AN: 44132

Ashkenazi Jewish (ASJ) AF: 0.0000771 AC: 2 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85952

European-Finnish (FIN) AF: 0.000695 AC: 37 AN: 53220

Middle Eastern (MID) AF: 0.00120 AC: 5 AN: 4180

European-Non Finnish (NFE) AF: 0.00165 AC: 1837 AN: 1110844

Other (OTH) AF: 0.00107 AC: 64 AN: 60068

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152140 Hom.: 0 Cov.: 31 AF XY: 0.00113 AC XY: 84 AN XY: 74380

African (AFR) AF: 0.000265 AC: 11 AN: 41474

American (AMR) AF: 0.00163 AC: 25 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00172 AC: 117 AN: 67986

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00152 Hom.: 1

Bravo AF: 0.00106

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00105 AC: 128

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.67
MPC		0.72
ClinPred		0.040	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.30
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs137878288; hg19: chr3-187446313; COSMIC: COSV51653480; COSMIC: COSV51653480;