3-187727409-A-G

Variant names:

• chr3-187727409-A-G
• rs3774309
• NM_001706.5:c.1541-511T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001706.5(BCL6):​c.1541-511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,228 control chromosomes in the GnomAD database, including 25,991 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 0.54 (25991 hom., cov: 34)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.1541-511T>C		intron	N/A	NP_001697.2
	BCL6	NM_001130845.2		c.1541-511T>C		intron	N/A	NP_001124317.1
	BCL6	NM_001134738.2		c.1540+951T>C		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.1541-511T>C		intron	N/A	ENSP00000384371.2
	BCL6	ENST00000232014.8	TSL:1	c.1541-511T>C		intron	N/A	ENSP00000232014.4
	BCL6	ENST00000450123.6	TSL:1	c.1540+951T>C		intron	N/A	ENSP00000413122.2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82127 AN: 152110 Hom.: 25979 Cov.: 34

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.597

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.540 AC: 82162 AN: 152228 Hom.: 25991 Cov.: 34 AF XY: 0.549 AC XY: 40894 AN XY: 74430

African (AFR) AF: 0.185 AC: 7669 AN: 41540

American (AMR) AF: 0.701 AC: 10734 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4135 AN: 5172

South Asian (SAS) AF: 0.655 AC: 3160 AN: 4828

European-Finnish (FIN) AF: 0.703 AC: 7454 AN: 10598

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44323 AN: 67998

Other (OTH) AF: 0.598 AC: 1263 AN: 2112

Alfa AF: 0.572 Hom.: 3507

Bravo AF: 0.526

Asia WGS AF: 0.668 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		1.2
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: rs3774309; hg19: chr3-187445197;