rs2229362

Variant names:

• chr3-187728423-C-T
• rs2229362
• NM_001706.5:c.1477G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-187728423-C-T
• chr3-187728423-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001706.5(BCL6):​c.1477G>A​(p.Ala493Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,610,620 control chromosomes in the GnomAD database, including 22,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (4580 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18278 hom.)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.463
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022749603).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

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.1477G>A	p.Ala493Thr	missense	Exon 6 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.1477G>A	p.Ala493Thr	missense	Exon 6 of 10	NP_001124317.1	P41182-1
	BCL6	NM_001134738.2		c.1477G>A	p.Ala493Thr	missense	Exon 6 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.1477G>A	p.Ala493Thr	missense	Exon 6 of 10	ENSP00000384371.2	P41182-1
	BCL6	ENST00000232014.8	TSL:1	c.1477G>A	p.Ala493Thr	missense	Exon 6 of 10	ENSP00000232014.4	P41182-1
	BCL6	ENST00000450123.6	TSL:1	c.1477G>A	p.Ala493Thr	missense	Exon 5 of 8	ENSP00000413122.2	P41182-2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32238 AN: 151906 Hom.: 4570 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.143 AC: 34854 AN: 244402 AF XY: 0.138

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.0709

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.150 AC: 218845 AN: 1458596 Hom.: 18278 Cov.: 32 AF XY: 0.148 AC XY: 107306 AN XY: 725228

African (AFR) AF: 0.423 AC: 14127 AN: 33380

American (AMR) AF: 0.107 AC: 4749 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3795 AN: 26000

East Asian (EAS) AF: 0.0804 AC: 3186 AN: 39624

South Asian (SAS) AF: 0.103 AC: 8777 AN: 85616

European-Finnish (FIN) AF: 0.105 AC: 5589 AN: 53274

Middle Eastern (MID) AF: 0.129 AC: 737 AN: 5692

European-Non Finnish (NFE) AF: 0.152 AC: 168713 AN: 1110500

Other (OTH) AF: 0.152 AC: 9172 AN: 60272

GnomAD4 genome AF: 0.212 AC: 32277 AN: 152024 Hom.: 4580 Cov.: 32 AF XY: 0.206 AC XY: 15285 AN XY: 74330

African (AFR) AF: 0.408 AC: 16918 AN: 41428

American (AMR) AF: 0.152 AC: 2330 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.0736 AC: 380 AN: 5162

South Asian (SAS) AF: 0.0932 AC: 449 AN: 4816

European-Finnish (FIN) AF: 0.0947 AC: 1003 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10201 AN: 67958

Other (OTH) AF: 0.190 AC: 401 AN: 2108

Alfa AF: 0.164 Hom.: 5276

Bravo AF: 0.226

TwinsUK AF: 0.147 AC: 544

ALSPAC AF: 0.159 AC: 611

ESP6500AA AF: 0.405 AC: 1784

ESP6500EA AF: 0.152 AC: 1308

ExAC AF: 0.147 AC: 17864

Asia WGS AF: 0.116 AC: 404 AN: 3478

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	0.089
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.46
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.038
Sift	Benign	0.42	T
Sift4G	Benign	0.42	T
Polyphen		0.0040	B
Vest4		0.098
MPC		0.17
ClinPred		0.00088	T
GERP RS		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.15
Mutation Taster		=97/3	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: rs2229362; hg19: chr3-187446211; COSMIC: COSV51650064; COSMIC: COSV51650064;