rs210139

Positions:

• chr6-33575632-A-C
• chr6-33575632-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001188.4(BAK1):​c.206+161T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,776 control chromosomes in the GnomAD database, including 16,171 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 0.45 (16171 hom., cov: 30)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAK1	NM_001188.4	c.206+161T>G		intron_variant		ENST00000374467.4	NP_001179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.206+161T>G		intron_variant		1	NM_001188.4	ENSP00000363591.3
BAK1	ENST00000442998.6	c.206+161T>G		intron_variant		1		ENSP00000391258.2
GGNBP1	ENST00000612409.1	n.362+168A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68637 AN: 151656 Hom.: 16152 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.453 AC: 68695 AN: 151776 Hom.: 16171 Cov.: 30 AF XY: 0.464 AC XY: 34383 AN XY: 74160

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.462

Alfa AF: 0.413 Hom.: 22945

Bravo AF: 0.452

Asia WGS AF: 0.688 AC: 2392 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs210139; hg19: chr6-33543409;