chr3-187726810-G-C

Variant names:

• chr3-187726810-G-C
• NM_001706.5:c.1629C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001706.5(BCL6):​c.1629C>G​(p.Asp543Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1629C>G	p.Asp543Glu	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.1629C>G	p.Asp543Glu	missense_variant	Exon 7 of 10	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.32	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.19
Sift	Benign	0.48	T;T
Sift4G	Benign	0.21	T;T
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.31		Gain of glycosylation at T540 (P = 0.034);Gain of glycosylation at T540 (P = 0.034);
MVP		0.57
MPC		0.44
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.27
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-187444598;