19-48955955-A-G

Variant names:

• chr19-48955955-A-G
• rs3817074
• NM_138761.4:c.233+122A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138761.4(BAX):​c.233+122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,288,394 control chromosomes in the GnomAD database, including 507,793 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 0.89 (59785 hom., cov: 30)
  • Exomes 𝑓: 0.89 (448008 hom.)
• Consequence: BAX NM_138761.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 8 publications found

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

ENSG00000305635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4	c.233+122A>G		intron_variant	Intron 3 of 5	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.233+122A>G		intron_variant	Intron 3 of 5	1	NM_138761.4	ENSP00000263262.9

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134683 AN: 151988 Hom.: 59739 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.871

GnomAD4 exome AF: 0.888 AC: 1008654 AN: 1136288 Hom.: 448008 Cov.: 15 AF XY: 0.890 AC XY: 495764 AN XY: 557332

African (AFR) AF: 0.891 AC: 22271 AN: 24990

American (AMR) AF: 0.833 AC: 15495 AN: 18598

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 16031 AN: 17492

East Asian (EAS) AF: 0.961 AC: 31709 AN: 33004

South Asian (SAS) AF: 0.946 AC: 53397 AN: 56434

European-Finnish (FIN) AF: 0.926 AC: 34451 AN: 37224

Middle Eastern (MID) AF: 0.897 AC: 2932 AN: 3268

European-Non Finnish (NFE) AF: 0.880 AC: 789303 AN: 896930

Other (OTH) AF: 0.891 AC: 43065 AN: 48348

GnomAD4 genome AF: 0.886 AC: 134787 AN: 152106 Hom.: 59785 Cov.: 30 AF XY: 0.888 AC XY: 66027 AN XY: 74334

African (AFR) AF: 0.887 AC: 36815 AN: 41490

American (AMR) AF: 0.840 AC: 12833 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3171 AN: 3468

East Asian (EAS) AF: 0.951 AC: 4902 AN: 5154

South Asian (SAS) AF: 0.949 AC: 4567 AN: 4812

European-Finnish (FIN) AF: 0.922 AC: 9777 AN: 10604

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59894 AN: 67990

Other (OTH) AF: 0.872 AC: 1841 AN: 2112

Alfa AF: 0.885 Hom.: 22039

Bravo AF: 0.878

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.54
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3817074; hg19: chr19-49459212;