chr19-48955847-A-G

Variant names:

• chr19-48955847-A-G
• rs1805419
• NM_138761.4:c.233+14A>G

Variant summary

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

The NM_138761.4(BAX):​c.233+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,563,434 control chromosomes in the GnomAD database, including 385,281 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 0.66 (33385 hom., cov: 28)
  • Exomes 𝑓: 0.70 (351896 hom.)
• Consequence: BAX NM_138761.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 39 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4	c.233+14A>G		intron_variant	Intron 3 of 5	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.233+14A>G		intron_variant	Intron 3 of 5	1	NM_138761.4	ENSP00000263262.9

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100105 AN: 151304 Hom.: 33376 Cov.: 28

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.664

GnomAD2 exomes AF: 0.671 AC: 145099 AN: 216292 AF XY: 0.678

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.831

Gnomad EAS exome AF: 0.595

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.720

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.704 AC: 994305 AN: 1412012 Hom.: 351896 Cov.: 51 AF XY: 0.705 AC XY: 491923 AN XY: 697676

African (AFR) AF: 0.585 AC: 18509 AN: 31640

American (AMR) AF: 0.578 AC: 21837 AN: 37756

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 19378 AN: 23322

East Asian (EAS) AF: 0.643 AC: 24977 AN: 38854

South Asian (SAS) AF: 0.658 AC: 53388 AN: 81142

European-Finnish (FIN) AF: 0.646 AC: 33222 AN: 51440

Middle Eastern (MID) AF: 0.794 AC: 4280 AN: 5388

European-Non Finnish (NFE) AF: 0.718 AC: 778356 AN: 1084506

Other (OTH) AF: 0.696 AC: 40358 AN: 57964

GnomAD4 genome AF: 0.661 AC: 100143 AN: 151422 Hom.: 33385 Cov.: 28 AF XY: 0.656 AC XY: 48504 AN XY: 73940

African (AFR) AF: 0.583 AC: 24037 AN: 41236

American (AMR) AF: 0.630 AC: 9578 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2866 AN: 3464

East Asian (EAS) AF: 0.595 AC: 3029 AN: 5088

South Asian (SAS) AF: 0.647 AC: 3089 AN: 4778

European-Finnish (FIN) AF: 0.627 AC: 6579 AN: 10498

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.718 AC: 48726 AN: 67836

Other (OTH) AF: 0.665 AC: 1402 AN: 2108

Alfa AF: 0.705 Hom.: 64473

Bravo AF: 0.659

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1805419; hg19: chr19-49459104; COSMIC: COSV53169467; COSMIC: COSV53169467;