chr3-187729913-C-A

Variant names:

• chr3-187729913-C-A
• rs61752081
• NM_001706.5:c.492G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

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
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.13
• Publications: 19 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 -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.

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.492G>T	p.Glu164Asp	missense	Exon 5 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.492G>T	p.Glu164Asp	missense	Exon 5 of 10	NP_001124317.1	P41182-1
	BCL6	NM_001134738.2		c.492G>T	p.Glu164Asp	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.492G>T	p.Glu164Asp	missense	Exon 5 of 10	ENSP00000384371.2	P41182-1
	BCL6	ENST00000232014.8	TSL:1	c.492G>T	p.Glu164Asp	missense	Exon 5 of 10	ENSP00000232014.4	P41182-1
	BCL6	ENST00000450123.6	TSL:1	c.492G>T	p.Glu164Asp	missense	Exon 4 of 8	ENSP00000413122.2	P41182-2

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3542 AN: 152160 Hom.: 39 Cov.: 32

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

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.: 35 AF XY: 0.0289 AC XY: 21002 AN XY: 727172

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: 2 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

GnomAD4 genome AF: 0.0232 AC: 3540 AN: 152278 Hom.: 39 Cov.: 32 AF XY: 0.0221 AC XY: 1644 AN XY: 74448

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: 0 AN: 5174

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.0245 AC: 260 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2253 AN: 68024

Other (OTH) AF: 0.0345 AC: 73 AN: 2116

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: 29

ESP6500EA AF: 0.0331 AC: 285

ExAC AF: 0.0206 AC: 2504

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0328

EpiControl AF: 0.0338

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.046
Sift	Benign	0.28	T
Sift4G	Benign	0.43	T
Polyphen		0.0070	B
Vest4		0.076
MutPred		0.11		Loss of glycosylation at P168 (P = 0.1164)
MPC		0.16
ClinPred		0.010	T
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)

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: rs61752081; hg19: chr3-187447701; COSMIC: COSV51652125; COSMIC: COSV51652125;