NM_001706.5:c.1252A>T

Variant names:

• chr3-187729153-T-A
• rs142387697
• NM_001706.5:c.1252A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001706.5(BCL6):​c.1252A>T​(p.Met418Leu) 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. 15/21 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: 32)
• Consequence: BCL6 NM_001706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070469975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1252A>T	p.Met418Leu	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.1252A>T	p.Met418Leu	missense_variant	Exon 5 of 10	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247214 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133490

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Benign	0.24	.;T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T;.;T;.
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.28	.;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.24	.;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.26
MutPred		0.26		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.24
MPC		0.16
ClinPred		0.046	T
GERP RS		1.6
Varity_R		0.034
gMVP		0.12

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: rs142387697; hg19: chr3-187446941;