6-136278253-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014739.3(BCLAF1):c.628G>A(p.Gly210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000163 in 1,603,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

BCLAF1
NM_014739.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.13

Publications

9 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066773593).

BP6

Variant 6-136278253-C-T is Benign according to our data. Variant chr6-136278253-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCLAF1	NM_014739.3 link	c.628G>A	p.Gly210Ser	missense_variant	Exon 4 of 13	ENST00000531224.6	NP_055554.1	Q9NYF8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCLAF1	ENST00000531224.6 link	c.628G>A	p.Gly210Ser	missense_variant	Exon 4 of 13	1	NM_014739.3	ENSP00000435210.1		Q9NYF8-1

Frequencies

GnomAD3 genomes

AF:

0.000976

AC:

146

AN:

149540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00120

Gnomad ASJ

AF:

0.000879

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00336

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.000491

GnomAD2 exomes

AF:

0.0104

AC:

2550

AN:

246102

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00580

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0000798

AC:

116

AN:

1453836

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

723224

show subpopulations

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

African (AFR)

AF:

0.0000598

AC:

AN:

33450

American (AMR)

AF:

0.0000449

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00178

AC:

AN:

51562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1106622

Other (OTH)

AF:

0.0000166

AC:

AN:

60088

⚠️ 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: 0.246

Heterozygous variant carriers

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:

0.000976

AC:

146

AN:

149658

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

73152

show subpopulations

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

African (AFR)

AF:

0.000338

AC:

AN:

41460

American (AMR)

AF:

0.00120

AC:

AN:

15032

Ashkenazi Jewish (ASJ)

AF:

0.000879

AC:

AN:

3414

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00336

AC:

AN:

10120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00113

AC:

AN:

66378

Other (OTH)

AF:

0.000485

AC:

AN:

2060

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.243

Heterozygous variant carriers

120

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:

0.00453

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0201

AC:

2445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 - 5% MAF in Finnish population. Both parents carry this variant in the heterozygous state - variants in this gene are unlikely to be related to patient phenotype. -

Dec 10, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

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

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

D;D;D;D;D;.;D;D

MetaRNN

Benign

0.0067

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

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

PhyloP100

4.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.8

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

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;D;D;D;D;.;.

Sift4G

Benign

0.12

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

Polyphen

1.0

D;D;.;D;D;D;.;.

Vest4

0.53

ClinPred

0.016

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.52

Mutation Taster

=74/26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over