rs541016998

Variant names:

• chr3-187728536-G-A
• rs541016998
• NM_001706.5:c.1364C>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.1364C>T​(p.Thr455Met) variant causes a missense change. The variant allele was found at a frequency of 0.000305 in 1,607,052 control chromosomes in the GnomAD database, including 2 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 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.15
• Publications: 2 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=0.0070768297).
• BS2: High AC in GnomAd4 at 27 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.1364C>T	p.Thr455Met	missense	Exon 6 of 10	NP_001697.2
	BCL6	NM_001130845.2		c.1364C>T	p.Thr455Met	missense	Exon 6 of 10	NP_001124317.1
	BCL6	NM_001134738.2		c.1364C>T	p.Thr455Met	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.1364C>T	p.Thr455Met	missense	Exon 6 of 10	ENSP00000384371.2
	BCL6	ENST00000232014.8	TSL:1	c.1364C>T	p.Thr455Met	missense	Exon 6 of 10	ENSP00000232014.4
	BCL6	ENST00000450123.6	TSL:1	c.1364C>T	p.Thr455Met	missense	Exon 5 of 8	ENSP00000413122.2

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000704 AC: 172 AN: 244166 AF XY: 0.000839

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.000514

GnomAD4 exome AF: 0.000318 AC: 463 AN: 1454844 Hom.: 2 Cov.: 32 AF XY: 0.000437 AC XY: 316 AN XY: 723808

African (AFR) AF: 0.0000608 AC: 2 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 43628

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25846

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39414

South Asian (SAS) AF: 0.00464 AC: 398 AN: 85772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4118

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1110208

Other (OTH) AF: 0.000584 AC: 35 AN: 59946

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74432

African (AFR) AF: 0.0000723 AC: 3 AN: 41516

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

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

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000938 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.000774 AC: 94

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.055	T
Sift4G	Benign	0.14	T
Polyphen		0.97	D
Vest4		0.44
MVP		0.37
MPC		0.39
ClinPred		0.083	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.30
Mutation Taster		=96/4	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: rs541016998; hg19: chr3-187446324; COSMIC: COSV51655301;