19-48960027-A-C

Position:

• chr19-48960027-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAX	NM_138761.4	c.370-783A>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.370-783A>C		intron_variant		1	NM_138761.4	ENSP00000263262	P1

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.359

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs7259013; hg19: chr19-49463284;