19-48957954-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138761.4(BAX):c.369+1621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 151,962 control chromosomes in the GnomAD database, including 50,819 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 0.81 (50819 hom., cov: 31)
• Consequence: BAX NM_138761.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAX	NM_138761.4	c.369+1621T>G		intron_variant		ENST00000345358.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAX	ENST00000345358.12	c.369+1621T>G		intron_variant		1	NM_138761.4	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123234 AN: 151844 Hom.: 50797 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.811 AC: 123295 AN: 151962 Hom.: 50819 Cov.: 31 AF XY: 0.816 AC XY: 60593 AN XY: 74274

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.818

Alfa AF: 0.810 Hom.: 5714

Bravo AF: 0.797

Asia WGS AF: 0.881 AC: 3064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.99
Dann	Benign	0.56

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: rs1010103; hg19: chr19-49461211;