3-187726842-G-T

Position:

• chr3-187726842-G-T

Variant summary

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

The NM_001706.5(BCL6):​c.1597C>A​(p.Leu533Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86

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/exons	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1597C>A	p.Leu533Ile	missense_variant	7/10	ENST00000406870.7	NP_001697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.1597C>A	p.Leu533Ile	missense_variant	7/10	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2024

The c.1597C>A (p.L533I) alteration is located in exon 7 (coding exon 5) of the BCL6 gene. This alteration results from a C to A substitution at nucleotide position 1597, causing the leucine (L) at amino acid position 533 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.23	T;T
Polyphen		0.99	D;D
Vest4		0.77
MutPred		0.38		Gain of glycosylation at S528 (P = 0.0234);Gain of glycosylation at S528 (P = 0.0234);
MVP		0.55
MPC		0.65
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.37
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-187444630;