19-48958048-T-C

Variant names:

• chr19-48958048-T-C
• rs2387583
• NM_138761.4:c.369+1715T>C

Variant summary

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

The NM_138761.4(BAX):​c.369+1715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 151,426 control chromosomes in the GnomAD database, including 53,804 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 0.84 (53804 hom., cov: 28)
• Consequence: BAX NM_138761.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138761.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	NM_138761.4	MANE Select	c.369+1715T>C		intron	N/A	NP_620116.1	Q07812-1
	BAX	NM_001291428.2		c.369+1715T>C		intron	N/A	NP_001278357.1
	BAX	NM_004324.4		c.369+1715T>C		intron	N/A	NP_004315.1	Q07812-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	ENST00000345358.12	TSL:1 MANE Select	c.369+1715T>C		intron	N/A	ENSP00000263262.9	Q07812-1
	BAX	ENST00000293288.12	TSL:1	c.369+1715T>C		intron	N/A	ENSP00000293288.8	Q07812-2
	BAX	ENST00000415969.6	TSL:1	c.369+1715T>C		intron	N/A	ENSP00000389971.2	Q07812-8

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127187 AN: 151310 Hom.: 53777 Cov.: 28

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.840 AC: 127259 AN: 151426 Hom.: 53804 Cov.: 28 AF XY: 0.844 AC XY: 62373 AN XY: 73918

African (AFR) AF: 0.752 AC: 30954 AN: 41178

American (AMR) AF: 0.821 AC: 12433 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3111 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4880 AN: 5156

South Asian (SAS) AF: 0.925 AC: 4444 AN: 4806

European-Finnish (FIN) AF: 0.909 AC: 9483 AN: 10432

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.872 AC: 59231 AN: 67944

Other (OTH) AF: 0.839 AC: 1760 AN: 2098

Alfa AF: 0.856 Hom.: 71396

Bravo AF: 0.830

Asia WGS AF: 0.887 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.84
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2387583; hg19: chr19-49461305;