Variant 17-7024475-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181844.4(BCL6B):c.476G>A(p.Gly159Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

BCL6B
NM_181844.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.429

Variant links:

Genes affected

BCL6B (HGNC:1002): (BCL6B transcription repressor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including regulation of gene expression; regulation of inflammatory response; and type 2 immune response. Predicted to be located in nucleus. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BCL6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037761986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL6B	NM_181844.4 linkuse as main transcript	c.476G>A	p.Gly159Asp	missense_variant	4/9	ENST00000293805.10	NP_862827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL6B	ENST00000293805.10 linkuse as main transcript	c.476G>A	p.Gly159Asp	missense_variant	4/9	1	NM_181844.4	ENSP00000293805	P1
BCL6B	ENST00000572216.1 linkuse as main transcript	n.384G>A		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249356

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000277

AC:

AN:

151620

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

AN XY:

73992

show subpopulations

Gnomad4 AFR

AF:

0.000631

Gnomad4 AMR

AF:

0.000920

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000961

Alfa

AF:

0.0000650

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.000794

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.476G>A (p.G159D) alteration is located in exon 4 (coding exon 3) of the BCL6B gene. This alteration results from a G to A substitution at nucleotide position 476, causing the glycine (G) at amino acid position 159 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.028

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.080

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.61

M_CAP

Benign

0.0025

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

MutationTaster

Benign

0.67

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.1

REVEL

Benign

0.042

Sift

Benign

0.51

Sift4G

Benign

0.56

Polyphen

0.0070

Vest4

0.16

MVP

0.51

MPC

0.54

ClinPred

0.026

GERP RS

4.1

Varity_R

0.044

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over