6-136272017-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_014739.3(BCLAF1):c.2021T>C(p.Val674Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000873 in 1,603,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

BCLAF1
NM_014739.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, BCLAF1

BP4

Computational evidence support a benign effect (MetaRNN=0.048296094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCLAF1	NM_014739.3 linkuse as main transcript	c.2021T>C	p.Val674Ala	missense_variant	8/13	ENST00000531224.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCLAF1	ENST00000531224.6 linkuse as main transcript	c.2021T>C	p.Val674Ala	missense_variant	8/13	1	NM_014739.3	P4	Q9NYF8-1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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:

0.000482

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248952

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000592

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000689

AC:

AN:

1452218

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.000137

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151040

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73742

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000133

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:

0.000482

Bravo

AF:

0.0000793

ExAC

AF:

0.0000165

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

Dec 09, 2023

The c.2021T>C (p.V674A) alteration is located in exon 8 (coding exon 6) of the BCLAF1 gene. This alteration results from a T to C substitution at nucleotide position 2021, causing the valine (V) at amino acid position 674 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.84

DEOGEN2

Benign

0.034

T;.;.;.;.;.;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

T;T;T;T;T;.;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.048

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.41

N;.;.;.;.;.;.;.

MutationTaster

Benign

0.97

N;N;N;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.35

N;N;N;N;N;N;.;N

REVEL

Benign

0.10

Sift

Benign

0.63

T;T;T;T;T;T;.;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;.

Polyphen

0.0

B;B;.;B;B;B;.;.

Vest4

0.36

MutPred

0.19

Loss of stability (P = 0.0305);.;Loss of stability (P = 0.0305);.;.;.;Loss of stability (P = 0.0305);.;

MVP

0.22

ClinPred

0.019

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

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