chr19-48961714-G-A

Variant names:

• chr19-48961714-G-A
• rs704243
• NM_138761.4:c.*78G>A

Variant summary

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

The NM_138761.4(BAX):​c.*78G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 1,067,090 control chromosomes in the GnomAD database, including 428,073 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 (59164 hom., cov: 23)
  • Exomes 𝑓: 0.89 (368909 hom.)
• Consequence: BAX NM_138761.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 16 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4	c.*78G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.*78G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_138761.4	ENSP00000263262.9

Frequencies

GnomAD3 genomes AF: 0.889 AC: 132878 AN: 149496 Hom.: 59118 Cov.: 23

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.904

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.877

GnomAD4 exome AF: 0.895 AC: 820996 AN: 917478 Hom.: 368909 Cov.: 12 AF XY: 0.897 AC XY: 416464 AN XY: 464466

African (AFR) AF: 0.892 AC: 18321 AN: 20542

American (AMR) AF: 0.836 AC: 22862 AN: 27342

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 18533 AN: 20086

East Asian (EAS) AF: 0.951 AC: 28890 AN: 30376

South Asian (SAS) AF: 0.935 AC: 62849 AN: 67184

European-Finnish (FIN) AF: 0.909 AC: 33820 AN: 37206

Middle Eastern (MID) AF: 0.905 AC: 4068 AN: 4494

European-Non Finnish (NFE) AF: 0.889 AC: 595704 AN: 670044

Other (OTH) AF: 0.894 AC: 35949 AN: 40204

GnomAD4 genome AF: 0.889 AC: 132980 AN: 149612 Hom.: 59164 Cov.: 23 AF XY: 0.890 AC XY: 64915 AN XY: 72942

African (AFR) AF: 0.894 AC: 36171 AN: 40480

American (AMR) AF: 0.854 AC: 12792 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3176 AN: 3458

East Asian (EAS) AF: 0.932 AC: 4623 AN: 4958

South Asian (SAS) AF: 0.937 AC: 4400 AN: 4696

European-Finnish (FIN) AF: 0.903 AC: 9273 AN: 10270

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.884 AC: 59709 AN: 67524

Other (OTH) AF: 0.877 AC: 1796 AN: 2048

Alfa AF: 0.885 Hom.: 22417

Bravo AF: 0.884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.5
DANN	Benign	0.89
PhyloP100		-0.40
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

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: rs704243; hg19: chr19-49464971; COSMIC: COSV53170523; COSMIC: COSV53170523;