rs5745582

Positions:

• chr6-33578721-C-T

Variant summary

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

The NM_001188.4(BAK1):​c.-31-1086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,026 control chromosomes in the GnomAD database, including 4,947 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 0.25 (4947 hom., cov: 32)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAK1	NM_001188.4	c.-31-1086G>A		intron_variant		ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4	c.-142-813G>A		intron_variant			XP_011513081.1
BAK1	XM_047419194.1	c.-31-1086G>A		intron_variant			XP_047275150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.-31-1086G>A		intron_variant		1	NM_001188.4	ENSP00000363591	P1
BAK1	ENST00000442998.6	c.-31-1086G>A		intron_variant		1		ENSP00000391258
GGNBP1	ENST00000612409.1	n.362+3257C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37732 AN: 151908 Hom.: 4936 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.248 AC: 37754 AN: 152026 Hom.: 4947 Cov.: 32 AF XY: 0.257 AC XY: 19108 AN XY: 74308

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.214

Alfa AF: 0.227 Hom.: 692

Bravo AF: 0.246

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.72

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: rs5745582; hg19: chr6-33546498;