ENST00000502487.5:n.499T>C

Variant names:

• chr19-48955313-T-C
• rs1009316
• ENST00000502487.5:n.499T>C

Variant summary

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

The ENST00000502487.5(BAX):​n.499T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 464,454 control chromosomes in the GnomAD database, including 170,940 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 (50886 hom., cov: 31)
  • Exomes 𝑓: 0.87 (120054 hom.)
• Consequence: BAX ENST00000502487.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4	c.35-235T>C		intron_variant	Intron 1 of 5	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.35-235T>C		intron_variant	Intron 1 of 5	1	NM_138761.4	ENSP00000263262.9

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123337 AN: 151870 Hom.: 50862 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.875 AC: 273371 AN: 312466 Hom.: 120054 Cov.: 4 AF XY: 0.877 AC XY: 140759 AN XY: 160558

African (AFR) AF: 0.655 AC: 5638 AN: 8602

American (AMR) AF: 0.807 AC: 6974 AN: 8644

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 9201 AN: 10256

East Asian (EAS) AF: 0.964 AC: 22911 AN: 23764

South Asian (SAS) AF: 0.916 AC: 12424 AN: 13566

European-Finnish (FIN) AF: 0.910 AC: 21120 AN: 23202

Middle Eastern (MID) AF: 0.858 AC: 1276 AN: 1488

European-Non Finnish (NFE) AF: 0.871 AC: 177456 AN: 203848

Other (OTH) AF: 0.857 AC: 16371 AN: 19096

GnomAD4 genome AF: 0.812 AC: 123401 AN: 151988 Hom.: 50886 Cov.: 31 AF XY: 0.816 AC XY: 60660 AN XY: 74296

African (AFR) AF: 0.652 AC: 27055 AN: 41480

American (AMR) AF: 0.812 AC: 12425 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4828 AN: 5102

South Asian (SAS) AF: 0.925 AC: 4446 AN: 4804

European-Finnish (FIN) AF: 0.909 AC: 9649 AN: 10614

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59191 AN: 67908

Other (OTH) AF: 0.819 AC: 1729 AN: 2110

Alfa AF: 0.835 Hom.: 4408

Bravo AF: 0.798

Asia WGS AF: 0.882 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		-1.2
PromoterAI		0.0096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1009316; hg19: chr19-49458570;