chr3-187724739-C-A

Position:

• chr3-187724739-C-A

Variant summary

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

The NM_001706.5(BCL6):​c.1977+202G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 691,196 control chromosomes in the GnomAD database, including 67,281 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 0.36 (11915 hom., cov: 32)
  • Exomes 𝑓: 0.44 (55366 hom.)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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]

BCL6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL6	NM_001706.5	c.1977+202G>T		intron_variant		ENST00000406870.7	NP_001697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.1977+202G>T		intron_variant		1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54191 AN: 151966 Hom.: 11913 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.444 AC: 239157 AN: 539112 Hom.: 55366 Cov.: 7 AF XY: 0.438 AC XY: 122209 AN XY: 278794

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.356 AC: 54192 AN: 152084 Hom.: 11915 Cov.: 32 AF XY: 0.361 AC XY: 26860 AN XY: 74314

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.388

Alfa AF: 0.429 Hom.: 10771

Bravo AF: 0.339

Asia WGS AF: 0.393 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.73

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: rs1474326; hg19: chr3-187442527;