rs561276

Variant names:

• chr6-33575339-C-T
• rs561276
• NM_001188.4:c.309G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001188.4(BAK1):​c.309G>A​(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,100 control chromosomes in the GnomAD database, including 487 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 0.036 (217 hom., cov: 32)
  • Exomes 𝑓: 0.010 (270 hom.)
• Consequence: BAK1 NM_001188.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39
• Publications: 7 publications found

Genes affected

BAK1 (HGNC:949): (BCL2 antagonist/killer 1) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. [provided by RefSeq, Jul 2008]

ENSG00000293518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-4.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001188.4. 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
	BAK1	NM_001188.4	MANE Select	c.309G>A	p.Thr103Thr	synonymous	Exon 4 of 6	NP_001179.1	Q16611-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAK1	ENST00000374467.4	TSL:1 MANE Select	c.309G>A	p.Thr103Thr	synonymous	Exon 4 of 6	ENSP00000363591.3	Q16611-1
	BAK1	ENST00000442998.6	TSL:1	c.309G>A	p.Thr103Thr	synonymous	Exon 4 of 7	ENSP00000391258.2	Q16611-2
	BAK1	ENST00000938018.1		c.486G>A	p.Thr162Thr	synonymous	Exon 4 of 6	ENSP00000608077.1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5418 AN: 152094 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.00909

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0154 AC: 3861 AN: 251438 AF XY: 0.0137

Gnomad AFR exome AF: 0.0980

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0270

Gnomad EAS exome AF: 0.00212

Gnomad FIN exome AF: 0.00222

Gnomad NFE exome AF: 0.00847

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0103 AC: 14990 AN: 1461888 Hom.: 270 Cov.: 32 AF XY: 0.0102 AC XY: 7404 AN XY: 727246

African (AFR) AF: 0.0987 AC: 3304 AN: 33480

American (AMR) AF: 0.0172 AC: 769 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 737 AN: 26136

East Asian (EAS) AF: 0.00151 AC: 60 AN: 39700

South Asian (SAS) AF: 0.0105 AC: 907 AN: 86256

European-Finnish (FIN) AF: 0.00260 AC: 139 AN: 53420

Middle Eastern (MID) AF: 0.0470 AC: 271 AN: 5768

European-Non Finnish (NFE) AF: 0.00703 AC: 7818 AN: 1112008

Other (OTH) AF: 0.0163 AC: 985 AN: 60396

GnomAD4 genome AF: 0.0357 AC: 5429 AN: 152212 Hom.: 217 Cov.: 32 AF XY: 0.0341 AC XY: 2540 AN XY: 74424

African (AFR) AF: 0.100 AC: 4152 AN: 41510

American (AMR) AF: 0.0235 AC: 359 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4816

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.00909 AC: 618 AN: 68008

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0185 Hom.: 23

Bravo AF: 0.0409

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.0106

EpiControl AF: 0.0114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-4.4
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: rs561276; hg19: chr6-33543116; COSMIC: COSV62349514;