NM_138761.4:c.69G>A

Variant names:

• chr19-48955582-G-A
• rs140986746
• NM_138761.4:c.69G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_138761.4(BAX):​c.69G>A​(p.Gly23Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,613,856 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00092 (4 hom.)
• Consequence: BAX NM_138761.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-48955582-G-A is Benign according to our data. Variant chr19-48955582-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 784551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138761.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	NM_138761.4	MANE Select	c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 6	NP_620116.1	Q07812-1
	BAX	NM_001291428.2		c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 6	NP_001278357.1
	BAX	NM_004324.4		c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 5	NP_004315.1	Q07812-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	ENST00000345358.12	TSL:1 MANE Select	c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 6	ENSP00000263262.9	Q07812-1
	BAX	ENST00000293288.12	TSL:1	c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 5	ENSP00000293288.8	Q07812-2
	BAX	ENST00000415969.6	TSL:1	c.69G>A	p.Gly23Gly	synonymous	Exon 2 of 6	ENSP00000389971.2	Q07812-8

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152038 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000665 AC: 167 AN: 251194 AF XY: 0.000729

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000809

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000921 AC: 1346 AN: 1461700 Hom.: 4 Cov.: 30 AF XY: 0.000904 AC XY: 657 AN XY: 727158

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.00168 AC: 75 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86216

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00106 AC: 1176 AN: 1111908

Other (OTH) AF: 0.000762 AC: 46 AN: 60386

GnomAD4 genome AF: 0.000572 AC: 87 AN: 152156 Hom.: 1 Cov.: 31 AF XY: 0.000524 AC XY: 39 AN XY: 74370

African (AFR) AF: 0.000241 AC: 10 AN: 41514

American (AMR) AF: 0.00111 AC: 17 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67986

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.000867 Hom.: 0

Bravo AF: 0.000759

EpiCase AF: 0.000436

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs140986746; hg19: chr19-49458839; COSMIC: COSV107353823;