rs1805419

chr19-48955847-A-Gchr19-48955847-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 19-48955847-A-G is Benign according to our data. Variant chr19-48955847-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
BAX	NM_138761.4	c.233+14A>G		intron_variant		ENST00000345358.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAX	ENST00000345358.12	c.233+14A>G		intron_variant		1	NM_138761.4	P1

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

GnomAD3 exomes AF: 0.671 AC: 145099 AN: 216292 Hom.: 49311 AF XY: 0.678 AC XY: 79239 AN XY: 116798

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 SAS exome AF: 0.659

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

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.831

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.696

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

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.665

Alfa AF: 0.710 Hom.: 51774

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805419; hg19: chr19-49459104; COSMIC: COSV53169467; COSMIC: COSV53169467;