Variant 6-136268287-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014739.3(BCLAF1):c.2272C>A(p.Pro758Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BCLAF1
NM_014739.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.03

Variant links:

Genes affected

BCLAF1 (HGNC:16863): (BCL2 associated transcription factor 1) This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BCLAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023156106).

BP6

Variant 6-136268287-G-T is Benign according to our data. Variant chr6-136268287-G-T is described in ClinVar as [Benign]. Clinvar id is 402421.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCLAF1	NM_014739.3 linkuse as main transcript	c.2272C>A	p.Pro758Thr	missense_variant	10/13	ENST00000531224.6	NP_055554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCLAF1	ENST00000531224.6 linkuse as main transcript	c.2272C>A	p.Pro758Thr	missense_variant	10/13	1	NM_014739.3	ENSP00000435210	P4	Q9NYF8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151776

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0671

AC:

15579

AN:

232134

Hom.:

AF XY:

0.0693

AC XY:

8691

AN XY:

125338

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0422

Gnomad EAS exome

AF:

0.00262

Gnomad SAS exome

AF:

0.0384

Gnomad FIN exome

AF:

0.0750

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0703

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00283

AC:

3924

AN:

1384952

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2227

AN XY:

689630

show subpopulations

Gnomad4 AFR exome

AF:

0.000489

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.00170

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74104

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.00

Alfa

AF:

0.113

Hom.:

545

ExAC

AF:

0.100

AC:

12147

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

BCLAF1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Benign

0.79

DEOGEN2

Benign

0.066

T;.;.;.;.;.

Eigen

Benign

-0.089

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

T;T;T;T;T;.

MetaRNN

Benign

0.0023

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.;.;.;.

MutationTaster

Benign

0.90

D;D;D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.046

Sift

Uncertain

0.0090

D;D;D;D;D;D

Sift4G

Benign

0.25

T;T;T;T;T;T

Polyphen

0.042

B;B;.;B;B;B

Vest4

0.26

ClinPred

0.016

GERP RS

3.7

Varity_R

0.068

gMVP

0.065

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