rs561276

chr6-33575339-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001188.4(BAK1):c.309G>A(p.Thr103=) 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

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]

GGNBP1 (HGNC:19427): (gametogenetin binding protein 1 (pseudogene)) This gene is the ortholog of the mouse gametogenetin-binding protein 1 gene. In human, the open reading frame is disrupted by a nonsense mutation after 8-aa; consequently, this gene is currently considered to be a unitary pseudogene in human even though it is functional in other mammals. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAK1	NM_001188.4	c.309G>A	p.Thr103=	synonymous_variant	4/6	ENST00000374467.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAK1	ENST00000374467.4	c.309G>A	p.Thr103=	synonymous_variant	4/6	1	NM_001188.4	P1
BAK1	ENST00000442998.6	c.309G>A	p.Thr103=	synonymous_variant	4/7	1
GGNBP1	ENST00000612409.1	n.249-12C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.0154 AC: 3861 AN: 251438 Hom.: 107 AF XY: 0.0137 AC XY: 1866 AN XY: 135894

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 SAS exome AF: 0.0105

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

Gnomad4 AFR exome AF: 0.0987

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.0282

Gnomad4 EAS exome AF: 0.00151

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.00260

Gnomad4 NFE exome AF: 0.00703

Gnomad4 OTH exome AF: 0.0163

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

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00519

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00909

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0168 Hom.: 21

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	2.2
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs561276; hg19: chr6-33543116; COSMIC: COSV62349514;