3-187724739-C-A

Variant names:

• chr3-187724739-C-A
• rs1474326
• NM_001706.5:c.1977+202G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.1977+202G>T		intron	N/A	NP_001697.2
	BCL6	NM_001130845.2		c.1977+202G>T		intron	N/A	NP_001124317.1
	BCL6	NM_001134738.2		c.1809+202G>T		intron	N/A	NP_001128210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.1977+202G>T		intron	N/A	ENSP00000384371.2
	BCL6	ENST00000232014.8	TSL:1	c.1977+202G>T		intron	N/A	ENSP00000232014.4
	BCL6	ENST00000450123.6	TSL:1	c.1809+202G>T		intron	N/A	ENSP00000413122.2

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

African (AFR) AF: 0.0882 AC: 1252 AN: 14198

American (AMR) AF: 0.398 AC: 7352 AN: 18468

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 6400 AN: 13838

East Asian (EAS) AF: 0.614 AC: 18432 AN: 30020

South Asian (SAS) AF: 0.332 AC: 15727 AN: 47384

European-Finnish (FIN) AF: 0.529 AC: 14605 AN: 27586

Middle Eastern (MID) AF: 0.405 AC: 864 AN: 2132

European-Non Finnish (NFE) AF: 0.455 AC: 162351 AN: 357050

Other (OTH) AF: 0.428 AC: 12174 AN: 28436

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

African (AFR) AF: 0.0909 AC: 3774 AN: 41520

American (AMR) AF: 0.382 AC: 5841 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3241 AN: 5136

South Asian (SAS) AF: 0.334 AC: 1610 AN: 4822

European-Finnish (FIN) AF: 0.536 AC: 5660 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30907 AN: 67966

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.408 Hom.: 15723

Bravo AF: 0.339

Asia WGS AF: 0.393 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1474326; hg19: chr3-187442527;