19-48955955-A-G

Position:

• chr19-48955955-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BAX	NM_138761.4	c.233+122A>G		intron_variant		ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.233+122A>G		intron_variant		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

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.916

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.926

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.891

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

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.949

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.872

Alfa AF: 0.886 Hom.: 13533

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs3817074; hg19: chr19-49459212;