chr3-187726755-C-G

Variant names:

• chr3-187726755-C-G
• rs77733730
• NM_001706.5:c.1684G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001706.5(BCL6):​c.1684G>C​(p.Ala562Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.00047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009470046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1684G>C	p.Ala562Pro	missense_variant	Exon 7 of 10	ENST00000406870.7	NP_001697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.1684G>C	p.Ala562Pro	missense_variant	Exon 7 of 10	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000472 AC: 687 AN: 1454268 Hom.: 0 Cov.: 31 AF XY: 0.000454 AC XY: 328 AN XY: 723024

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.000710

Gnomad4 ASJ exome AF: 0.000471

Gnomad4 EAS exome AF: 0.00153

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00674

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome Cov.: 33

ExAC AF: 0.0304 AC: 3688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	.;T
MetaRNN	Benign	0.0095	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.098	T;T
Polyphen		1.0	D;D
Vest4		0.35
MPC		2.0
ClinPred		0.0086	T
GERP RS		5.6
Varity_R		0.73
gMVP		0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs77733730; hg19: chr3-187444543; COSMIC: COSV51649718; COSMIC: COSV51649718;