6-136268287-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014739.3(BCLAF1):c.2272C>T(p.Pro758Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,564,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P758T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

BCLAF1
NM_014739.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027041227).

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>T	p.Pro758Ser	missense	Exon 10 of 13	NP_055554.1
BCLAF1	NM_001386700.1		c.2272C>T	p.Pro758Ser	missense	Exon 11 of 14	NP_001373629.1
BCLAF1	NM_001386701.1		c.2272C>T	p.Pro758Ser	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>T	p.Pro758Ser	missense	Exon 10 of 13	ENSP00000435210.1
BCLAF1	ENST00000527759.5	TSL:1	c.2266C>T	p.Pro756Ser	missense	Exon 10 of 13	ENSP00000434826.1
BCLAF1	ENST00000530767.5	TSL:1	c.1753C>T	p.Pro585Ser	missense	Exon 10 of 13	ENSP00000436501.1

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000354

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000254

AC:

AN:

232134

AF XY:

0.000263

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.000528

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000345

Gnomad OTH exome

AF:

0.000358

GnomAD4 exome

AF:

0.000308

AC:

435

AN:

1412628

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

232

AN XY:

703422

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32826

American (AMR)

AF:

0.000236

AC:

AN:

42448

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

25450

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39526

South Asian (SAS)

AF:

0.000274

AC:

AN:

84026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52332

Middle Eastern (MID)

AF:

0.00110

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.000316

AC:

339

AN:

1071950

Other (OTH)

AF:

0.000410

AC:

AN:

58602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000296

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41514

American (AMR)

AF:

0.000525

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000354

AC:

AN:

67790

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000444

Hom.:

1306

Bravo

AF:

0.000291

ExAC

AF:

0.000338

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 14, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2272C>T (p.P758S) alteration is located in exon 10 (coding exon 8) of the BCLAF1 gene. This alteration results from a C to T substitution at nucleotide position 2272, causing the proline (P) at amino acid position 758 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.039

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

M_CAP

Benign

0.0084

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.060

PhyloP100

4.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.22

REVEL

Benign

0.073

Sift

Benign

0.89

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.30

MutPred

0.39

Gain of phosphorylation at P758 (P = 0)

MVP

0.31

ClinPred

0.021

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.049

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over