3-187729244-G-C

Variant names:

• chr3-187729244-G-C
• rs1056932
• NM_001706.5:c.1161C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001706.5(BCL6):​c.1161C>G​(p.Asn387Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 31)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27519926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1161C>G	p.Asn387Lys	missense_variant	Exon 5 of 10	ENST00000406870.7	NP_001697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.1161C>G	p.Asn387Lys	missense_variant	Exon 5 of 10	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	.;T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T;.;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.45	.;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.060	.;T;T;T
Sift4G	Benign	0.94	T;T;T;T
Polyphen		0.036	.;B;B;.
Vest4		0.37
MutPred		0.26		Gain of ubiquitination at N387 (P = 0.0177);Gain of ubiquitination at N387 (P = 0.0177);Gain of ubiquitination at N387 (P = 0.0177);Gain of ubiquitination at N387 (P = 0.0177);
MVP		0.28
MPC		0.21
ClinPred		0.12	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.45

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: rs1056932; hg19: chr3-187447032;