19-48955313-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000502487.5(BAX):​n.499T>G 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 0.0000452 in 464,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000045 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502487.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	NM_138761.4	MANE Select	c.35-235T>G		intron	N/A	NP_620116.1
	BAX	NM_001291428.2		c.35-235T>G		intron	N/A	NP_001278357.1
	BAX	NM_004324.4		c.35-235T>G		intron	N/A	NP_004315.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	ENST00000502487.5	TSL:1	n.499T>G		non_coding_transcript_exon	Exon 1 of 5
	BAX	ENST00000345358.12	TSL:1 MANE Select	c.35-235T>G		intron	N/A	ENSP00000263262.9
	BAX	ENST00000293288.12	TSL:1	c.35-235T>G		intron	N/A	ENSP00000293288.8

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151908 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.0000448 AC: 14 AN: 312726 Hom.: 0 Cov.: 4 AF XY: 0.0000311 AC XY: 5 AN XY: 160688

African (AFR) AF: 0.00 AC: 0 AN: 8614

American (AMR) AF: 0.000347 AC: 3 AN: 8656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10262

East Asian (EAS) AF: 0.00 AC: 0 AN: 23772

South Asian (SAS) AF: 0.00 AC: 0 AN: 13598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1488

European-Non Finnish (NFE) AF: 0.0000490 AC: 10 AN: 204016

Other (OTH) AF: 0.0000523 AC: 1 AN: 19108

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151908 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74190

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.000262 AC: 4 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67922

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 4408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.35
PhyloP100		-1.2
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;