chr19-48958048-T-C

Position:

• chr19-48958048-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAX	NM_138761.4	c.369+1715T>C		intron_variant		ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.369+1715T>C		intron_variant		1	NM_138761.4	ENSP00000263262.9

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

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.839

Alfa AF: 0.859 Hom.: 55355

Bravo AF: 0.830

Asia WGS AF: 0.887 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs2387583; hg19: chr19-49461305;