3-187733921-C-T

Variant names:

• chr3-187733921-C-T
• rs1880099
• NM_001706.5:c.-10-218G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.-10-218G>A		intron	N/A	NP_001697.2
	BCL6	NM_001130845.2		c.-10-218G>A		intron	N/A	NP_001124317.1	P41182-1
	BCL6	NM_001134738.2		c.-10-218G>A		intron	N/A	NP_001128210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.-10-218G>A		intron	N/A	ENSP00000384371.2	P41182-1
	BCL6	ENST00000232014.8	TSL:1	c.-10-218G>A		intron	N/A	ENSP00000232014.4	P41182-1
	BCL6	ENST00000450123.6	TSL:1	c.-10-218G>A		intron	N/A	ENSP00000413122.2	P41182-2

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

African (AFR) AF: 0.146 AC: 1710 AN: 11720

American (AMR) AF: 0.602 AC: 10904 AN: 18100

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 8534 AN: 12620

East Asian (EAS) AF: 0.738 AC: 20433 AN: 27674

South Asian (SAS) AF: 0.615 AC: 27911 AN: 45348

European-Finnish (FIN) AF: 0.649 AC: 16077 AN: 24778

Middle Eastern (MID) AF: 0.644 AC: 1315 AN: 2042

European-Non Finnish (NFE) AF: 0.617 AC: 152539 AN: 247412

Other (OTH) AF: 0.601 AC: 14203 AN: 23636

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

African (AFR) AF: 0.143 AC: 5925 AN: 41454

American (AMR) AF: 0.577 AC: 8792 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2343 AN: 3458

East Asian (EAS) AF: 0.749 AC: 3843 AN: 5130

South Asian (SAS) AF: 0.620 AC: 2983 AN: 4812

European-Finnish (FIN) AF: 0.648 AC: 6776 AN: 10462

Middle Eastern (MID) AF: 0.631 AC: 183 AN: 290

European-Non Finnish (NFE) AF: 0.614 AC: 41644 AN: 67806

Other (OTH) AF: 0.547 AC: 1156 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.37
PhyloP100		-0.13
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: rs1880099; hg19: chr3-187451709; COSMIC: COSV51653962; COSMIC: COSV51653962;