3-187727409-A-G

Position:

• chr3-187727409-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL6	NM_001706.5	c.1541-511T>C		intron_variant		ENST00000406870.7
LOC100131635	NR_034062.1	n.294-4962A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL6	ENST00000406870.7	c.1541-511T>C		intron_variant		1	NM_001706.5	P1
	ENST00000449623.5	n.347-6115A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.598

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.57

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: rs3774309; hg19: chr3-187445197;