NM_001706.5:c.1217G>A

Variant names:

• chr3-187729188-C-T
• rs369842677
• NM_001706.5:c.1217G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001706.5(BCL6):​c.1217G>A​(p.Arg406Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,574,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08916044).
• BS2: High AC in GnomAdExome4 at 21 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.1217G>A	p.Arg406Gln	missense	Exon 5 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.1217G>A	p.Arg406Gln	missense	Exon 5 of 10	NP_001124317.1	P41182-1
	BCL6	NM_001134738.2		c.1217G>A	p.Arg406Gln	missense	Exon 5 of 9	NP_001128210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.1217G>A	p.Arg406Gln	missense	Exon 5 of 10	ENSP00000384371.2	P41182-1
	BCL6	ENST00000232014.8	TSL:1	c.1217G>A	p.Arg406Gln	missense	Exon 5 of 10	ENSP00000232014.4	P41182-1
	BCL6	ENST00000450123.6	TSL:1	c.1217G>A	p.Arg406Gln	missense	Exon 4 of 8	ENSP00000413122.2	P41182-2

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 4 AN: 149674 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000987

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245638 AF XY: 0.00000753

Gnomad AFR exome AF: 0.0000630

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 21 AN: 1424956 Hom.: 0 Cov.: 31 AF XY: 0.0000198 AC XY: 14 AN XY: 707732

African (AFR) AF: 0.0000307 AC: 1 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 42468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 38102

South Asian (SAS) AF: 0.00 AC: 0 AN: 79720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.0000156 AC: 17 AN: 1090930

Other (OTH) AF: 0.0000513 AC: 3 AN: 58460

GnomAD4 genome AF: 0.0000267 AC: 4 AN: 149674 Hom.: 0 Cov.: 32 AF XY: 0.0000410 AC XY: 3 AN XY: 73126

African (AFR) AF: 0.0000987 AC: 4 AN: 40546

American (AMR) AF: 0.00 AC: 0 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 5018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67106

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.0000261 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.14	N
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.073
Sift	Benign	0.75	T
Sift4G	Benign	0.62	T
Polyphen		0.059	B
Vest4		0.14
MutPred		0.32		Gain of glycosylation at Y408 (P = 0.0011)
MVP		0.21
MPC		0.21
ClinPred		0.099	T
GERP RS		5.6
Varity_R		0.050
gMVP		0.20
Mutation Taster		=94/6	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: rs369842677; hg19: chr3-187446976; COSMIC: COSV51652397; COSMIC: COSV51652397;