3-187738921-T-G

Variant names:

• chr3-187738921-T-G
• rs3733017
• NM_001706.5:c.-49-4014A>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.-49-4014A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,174 control chromosomes in the GnomAD database, including 516 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 0.072 (516 hom., cov: 32)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL6	NM_001706.5	c.-49-4014A>C		intron_variant	Intron 1 of 9	ENST00000406870.7	NP_001697.2
BCL6	NM_001134738.2	c.-49-4014A>C		intron_variant	Intron 1 of 8		NP_001128210.1
BCL6	XM_047448655.1	c.-49-4014A>C		intron_variant	Intron 1 of 9		XP_047304611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL6	ENST00000406870.7	c.-49-4014A>C		intron_variant	Intron 1 of 9	1	NM_001706.5	ENSP00000384371.2

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10997 AN: 152056 Hom.: 516 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0723 AC: 11008 AN: 152174 Hom.: 516 Cov.: 32 AF XY: 0.0742 AC XY: 5519 AN XY: 74394

African (AFR) AF: 0.0791 AC: 3282 AN: 41514

American (AMR) AF: 0.0538 AC: 822 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5170

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1187 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3915 AN: 67988

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0622 Hom.: 652

Bravo AF: 0.0694

Asia WGS AF: 0.122 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.40
PhyloP100		-0.77
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: rs3733017; hg19: chr3-187456709;