19-48961106-C-T

Variant names:

• chr19-48961106-C-T
• rs4645900
• ENST00000293288.12:c.*9C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000293288.12(BAX):​c.*9C>T variant causes a 3 prime UTR 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 ENST00000293288.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• leukemia, acute lymphocytic, susceptibility to, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000305635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAX	NM_138761.4	c.474+192C>T		intron_variant	Intron 5 of 5	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12	c.474+192C>T		intron_variant	Intron 5 of 5	1	NM_138761.4	ENSP00000263262.9

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3463 AN: 152102 Hom.: 54 Cov.: 31

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

GnomAD2 exomes AF: 0.0281 AC: 6098 AN: 216786 AF XY: 0.0306

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 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.: 36 AF XY: 0.0326 AC XY: 22927 AN XY: 702280

African (AFR) AF: 0.00480 AC: 159 AN: 33152

American (AMR) AF: 0.0200 AC: 868 AN: 43498

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 1170 AN: 24274

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39276

South Asian (SAS) AF: 0.0383 AC: 3154 AN: 82252

European-Finnish (FIN) AF: 0.0124 AC: 497 AN: 40082

Middle Eastern (MID) AF: 0.0431 AC: 243 AN: 5642

European-Non Finnish (NFE) AF: 0.0346 AC: 37830 AN: 1093296

Other (OTH) AF: 0.0295 AC: 1743 AN: 59056

GnomAD4 genome AF: 0.0227 AC: 3457 AN: 152220 Hom.: 53 Cov.: 31 AF XY: 0.0223 AC XY: 1658 AN XY: 74422

African (AFR) AF: 0.00592 AC: 246 AN: 41532

American (AMR) AF: 0.0240 AC: 367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4826

European-Finnish (FIN) AF: 0.00745 AC: 79 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0348 AC: 2368 AN: 68008

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0333 Hom.: 195

Bravo AF: 0.0232

Asia WGS AF: 0.0170 AC: 61 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
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4645900; hg19: chr19-49464363;