dbSNP rs7259013: BAX:c.370-783A>C (chr19-48960027-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138761.4(BAX):c.370-783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 147,570 control chromosomes in the GnomAD database, including 8,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8695 hom., cov: 25)

Consequence

BAX
NM_138761.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.186

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4 link	c.370-783A>C		intron_variant	Intron 4 of 5	ENST00000345358.12	NP_620116.1	Q07812-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12 link	c.370-783A>C		intron_variant	Intron 4 of 5	1	NM_138761.4	ENSP00000263262.9		Q07812-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

50383

AN:

147484

Hom.:

8688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.425

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.342

AC:

50412

AN:

147570

Hom.:

8695

Cov.:

AF XY:

0.336

AC XY:

23999

AN XY:

71520

show subpopulations

African (AFR)

AF:

0.296

AC:

11802

AN:

39920

American (AMR)

AF:

0.329

AC:

4847

AN:

14748

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1486

AN:

3450

East Asian (EAS)

AF:

0.261

AC:

1311

AN:

5016

South Asian (SAS)

AF:

0.264

AC:

1230

AN:

4662

European-Finnish (FIN)

AF:

0.292

AC:

2686

AN:

9192

Middle Eastern (MID)

AF:

0.437

AC:

124

AN:

284

European-Non Finnish (NFE)

AF:

0.384

AC:

25866

AN:

67382

Other (OTH)

AF:

0.359

AC:

724

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1526

3052

4579

6105

7631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.373

Hom.:

2511

Bravo

AF:

0.346

Asia WGS

AF:

0.230

AC:

800

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.4

(source)

DANN

Benign

0.88

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over