3-187736943-C-T

Variant names:

• chr3-187736943-C-T
• rs3774304
• NM_001706.5:c.-49-2036G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001706.5(BCL6):​c.-49-2036G>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.-49-2036G>A		intron_variant	Intron 1 of 9	ENST00000406870.7	NP_001697.2
BCL6	XM_005247694.5	c.-50+654G>A		intron_variant	Intron 1 of 9		XP_005247751.1
BCL6	XM_047448655.1	c.-49-2036G>A		intron_variant	Intron 1 of 9		XP_047304611.1
BCL6	XM_011513062.4	c.-49-2036G>A		intron_variant	Intron 1 of 8		XP_011511364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.-49-2036G>A		intron_variant	Intron 1 of 9	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 24

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3774304; hg19: chr3-187454731;