chr19-48960027-A-C

Variant names:

• chr19-48960027-A-C
• rs7259013
• NM_138761.4:c.370-783A>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.370-783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 147,570 control chromosomes in the GnomAD database, including 8,695 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 0.34 (8695 hom., cov: 25)
• Consequence: BAX NM_138761.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 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.370-783A>C		intron	N/A	NP_620116.1	Q07812-1
	BAX	NM_001291428.2		c.370-783A>C		intron	N/A	NP_001278357.1
	BAX	NM_004324.4		c.370-783A>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.370-783A>C		intron	N/A	ENSP00000263262.9	Q07812-1
	BAX	ENST00000293288.12	TSL:1	c.370-783A>C		intron	N/A	ENSP00000293288.8	Q07812-2
	BAX	ENST00000415969.6	TSL:1	c.370-783A>C		intron	N/A	ENSP00000389971.2	Q07812-8

Frequencies

GnomAD3 genomes AF: 0.342 AC: 50383 AN: 147484 Hom.: 8688 Cov.: 25

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.425

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.342 AC: 50412 AN: 147570 Hom.: 8695 Cov.: 25 AF XY: 0.336 AC XY: 23999 AN XY: 71520

African (AFR) AF: 0.296 AC: 11802 AN: 39920

American (AMR) AF: 0.329 AC: 4847 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1486 AN: 3450

East Asian (EAS) AF: 0.261 AC: 1311 AN: 5016

South Asian (SAS) AF: 0.264 AC: 1230 AN: 4662

European-Finnish (FIN) AF: 0.292 AC: 2686 AN: 9192

Middle Eastern (MID) AF: 0.437 AC: 124 AN: 284

European-Non Finnish (NFE) AF: 0.384 AC: 25866 AN: 67382

Other (OTH) AF: 0.359 AC: 724 AN: 2018

Alfa AF: 0.373 Hom.: 2511

Bravo AF: 0.346

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.88
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7259013; hg19: chr19-49463284;