Variant 17-7024096-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_181844.4(BCL6B):c.193T>C(p.Ser65Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCL6B
NM_181844.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL6B	NM_181844.4 linkuse as main transcript	c.193T>C	p.Ser65Pro	missense_variant	3/9	ENST00000293805.10	NP_862827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BCL6B	ENST00000293805.10 linkuse as main transcript	c.193T>C	p.Ser65Pro	missense_variant	3/9	1	NM_181844.4	ENSP00000293805	P1
BCL6B	ENST00000576705.1 linkuse as main transcript	c.193T>C	p.Ser65Pro	missense_variant	3/3	4		ENSP00000460071
BCL6B	ENST00000573503.1 linkuse as main transcript	c.193T>C	p.Ser65Pro	missense_variant	2/2	2		ENSP00000460282
BCL6B	ENST00000572216.1 linkuse as main transcript	n.225-124T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 28, 2024

The c.193T>C (p.S65P) alteration is located in exon 3 (coding exon 2) of the BCL6B gene. This alteration results from a T to C substitution at nucleotide position 193, causing the serine (S) at amino acid position 65 to be replaced by a proline (P). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

D;T;T

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Uncertain

-0.021

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

0.83

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Uncertain

0.51

Sift

Benign

0.064

T;.;.

Sift4G

Benign

0.18

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.83

MutPred

0.81

Loss of methylation at R68 (P = 0.1219);Loss of methylation at R68 (P = 0.1219);Loss of methylation at R68 (P = 0.1219);

MVP

0.90

MPC

1.4

ClinPred

0.96

GERP RS

5.2

Varity_R

0.61

gMVP

0.92

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