Variant 19-48961106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000345358.12(BAX):c.474+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,572,748 control chromosomes in the GnomAD database, including 919 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 0.023 ( 53 hom., cov: 31)

Exomes 𝑓: 0.032 ( 866 hom. )

Consequence

BAX
ENST00000345358.12 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3457/152220) while in subpopulation NFE AF= 0.0348 (2368/68008). AF 95% confidence interval is 0.0337. There are 53 homozygotes in gnomad4. There are 1658 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3457 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAX	NM_138761.4 linkuse as main transcript	c.474+192C>T		intron_variant		ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12 linkuse as main transcript	c.474+192C>T		intron_variant		1	NM_138761.4	ENSP00000263262	P1	Q07812-1

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3463

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00594

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.00745

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0281

AC:

6098

AN:

216786

Hom.:

124

AF XY:

0.0306

AC XY:

3601

AN XY:

117770

show subpopulations

Gnomad AFR exome

AF:

0.00531

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0527

Gnomad EAS exome

AF:

0.000499

Gnomad SAS exome

AF:

0.0379

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0321

AC:

45670

AN:

1420528

Hom.:

866

Cov.:

AF XY:

0.0326

AC XY:

22927

AN XY:

702280

show subpopulations

Gnomad4 AFR exome

AF:

0.00480

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0482

Gnomad4 EAS exome

AF:

0.000153

Gnomad4 SAS exome

AF:

0.0383

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.0346

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0227

AC:

3457

AN:

152220

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.00745

Gnomad4 NFE

AF:

0.0348

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0342

Hom.:

165

Bravo

AF:

0.0232

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.58

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over