chr19-48960990-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004324.4(BAX):c.550G>A(p.Ala184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,292,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

BAX
NM_004324.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.247

Publications

3 publications found

Variant links:

Genes affected

BAX (HGNC:959): (BCL2 associated X, apoptosis regulator) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Dec 2019]

BAX Gene-Disease associations (from GenCC):

leukemia, acute lymphocytic, susceptibility to, 1
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

BAX links:

ENSG00000305635 (HGNC:):

ENSG00000305635 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08016494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004324.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAX	NM_138761.4	MANE Select	c.474+76G>A		intron	N/A	NP_620116.1	Q07812-1
BAX	NM_004324.4		c.550G>A	p.Ala184Thr	missense	Exon 5 of 5	NP_004315.1	Q07812-2
BAX	NM_001291429.2		c.439G>A	p.Ala147Thr	missense	Exon 4 of 4	NP_001278358.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAX	ENST00000293288.12	TSL:1	c.550G>A	p.Ala184Thr	missense	Exon 5 of 5	ENSP00000293288.8	Q07812-2
BAX	ENST00000539787.2	TSL:1	c.316G>A	p.Ala106Thr	missense	Exon 3 of 3	ENSP00000441413.2	I6LPK7
BAX	ENST00000345358.12	TSL:1 MANE Select	c.474+76G>A		intron	N/A	ENSP00000263262.9	Q07812-1

Frequencies

GnomAD3 genomes

AF:

0.0000698

AC:

AN:

143298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000689

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:

0.0000245

AC:

AN:

245292

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1149678

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

576298

show subpopulations

African (AFR)

AF:

0.000311

AC:

AN:

25698

American (AMR)

AF:

0.0000768

AC:

AN:

39044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18396

East Asian (EAS)

AF:

0.00

AC:

AN:

23740

South Asian (SAS)

AF:

0.00

AC:

AN:

81870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4556

European-Non Finnish (NFE)

AF:

0.00000684

AC:

AN:

877626

Other (OTH)

AF:

0.000114

AC:

AN:

43900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.0000698

AC:

AN:

143298

Hom.:

Cov.:

AF XY:

0.0000861

AC XY:

AN XY:

69660

show subpopulations

African (AFR)

AF:

0.000228

AC:

AN:

39396

American (AMR)

AF:

0.0000689

AC:

AN:

14510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4260

South Asian (SAS)

AF:

0.00

AC:

AN:

3960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65500

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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:

0.00

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000465

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.95

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.30

M_CAP

Benign

0.0031

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

PhyloP100

-0.25

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.020

REVEL

Benign

0.047

Sift

Uncertain

0.020

Sift4G

Benign

0.074

Polyphen

0.98

Vest4

0.12

MVP

0.31

MPC

0.18

ClinPred

0.16

GERP RS

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.11

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over