3-187733921-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001706.5(BCL6):c.-10-218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 565,004 control chromosomes in the GnomAD database, including 101,492 homozygotes. 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: 𝑓 0.49 (21770 hom., cov: 33)
  • Exomes 𝑓: 0.61 (79722 hom.)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL6	NM_001706.5	c.-10-218G>A		intron_variant		ENST00000406870.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL6	ENST00000406870.7	c.-10-218G>A		intron_variant		1	NM_001706.5	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74325 AN: 151558 Hom.: 21765 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.614 AC: 253626 AN: 413330 Hom.: 79722 AF XY: 0.614 AC XY: 134164 AN XY: 218450

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.490 AC: 74346 AN: 151674 Hom.: 21770 Cov.: 33 AF XY: 0.498 AC XY: 36871 AN XY: 74094

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.547

Alfa AF: 0.526 Hom.: 2905

Bravo AF: 0.474

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.6
Dann	Benign	0.37

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: rs1880099; hg19: chr3-187451709; COSMIC: COSV51653962; COSMIC: COSV51653962;