rs1009316

Positions:

• chr19-48955313-T-C
• chr19-48955313-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000345358.12(BAX):​c.35-235T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 464,454 control chromosomes in the GnomAD database, including 170,940 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 0.81 (50886 hom., cov: 31)
  • Exomes 𝑓: 0.87 (120054 hom.)
• Consequence: BAX ENST00000345358.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.86).
• 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.35-235T>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.35-235T>C		intron_variant		1	NM_138761.4	ENSP00000263262	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123337 AN: 151870 Hom.: 50862 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.875 AC: 273371 AN: 312466 Hom.: 120054 Cov.: 4 AF XY: 0.877 AC XY: 140759 AN XY: 160558

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.897

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 0.910

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.857

GnomAD4 genome AF: 0.812 AC: 123401 AN: 151988 Hom.: 50886 Cov.: 31 AF XY: 0.816 AC XY: 60660 AN XY: 74296

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.812

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: 0.819

Alfa AF: 0.835 Hom.: 4408

Bravo AF: 0.798

Asia WGS AF: 0.882 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.40
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

Publications

LitVar

Other links and lift over

dbSNP: rs1009316; hg19: chr19-49458570;