6-136268287-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P758S) has been classified as Uncertain significance.

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

Publications

14 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 402421.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014739.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCLAF1	NM_014739.3	MANE Select	c.2272C>A	p.Pro758Thr	missense	Exon 10 of 13	NP_055554.1
BCLAF1	NM_001386700.1		c.2272C>A	p.Pro758Thr	missense	Exon 11 of 14	NP_001373629.1
BCLAF1	NM_001386701.1		c.2272C>A	p.Pro758Thr	missense	Exon 11 of 14	NP_001373630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.2272C>A	p.Pro758Thr	missense	Exon 10 of 13	ENSP00000435210.1
BCLAF1	ENST00000527759.5	TSL:1	c.2266C>A	p.Pro756Thr	missense	Exon 10 of 13	ENSP00000434826.1
BCLAF1	ENST00000530767.5	TSL:1	c.1753C>A	p.Pro585Thr	missense	Exon 10 of 13	ENSP00000436501.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151776

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0671

AC:

15579

AN:

232134

AF XY:

0.0693

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000489

AC:

AN:

32752

American (AMR)

AF:

0.00182

AC:

AN:

42248

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.00117

AC:

AN:

83530

European-Finnish (FIN)

AF:

0.00152

AC:

AN:

51994

Middle Eastern (MID)

AF:

0.00166

AC:

AN:

5432

European-Non Finnish (NFE)

AF:

0.00332

AC:

3478

AN:

1046364

Other (OTH)

AF:

0.00214

AC:

124

AN:

57846

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

533

1067

1600

2134

2667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67796

Other (OTH)

AF:

0.00

AC:

AN:

2084

Alfa

AF:

0.117

Hom.:

1306

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

May 30, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.066

Eigen

Benign

-0.089

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

4.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.046

Sift

Uncertain

0.0090

Sift4G

Benign

0.25

Polyphen

0.042

Vest4

0.26

ClinPred

0.016

GERP RS

3.7

Varity_R

0.068

gMVP

0.065

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over