6-33579060-T-C

Variant names:

• chr6-33579060-T-C
• rs210142
• NM_001188.4:c.-32+965A>G

Variant summary

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

The NM_001188.4(BAK1):​c.-32+965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,170 control chromosomes in the GnomAD database, including 41,826 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 0.74 (41826 hom., cov: 33)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAK1	NM_001188.4	c.-32+965A>G		intron_variant	Intron 1 of 5	ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4	c.-143+965A>G		intron_variant	Intron 1 of 6		XP_011513081.1
BAK1	XM_047419194.1	c.-32+965A>G		intron_variant	Intron 1 of 4		XP_047275150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.-32+965A>G		intron_variant	Intron 1 of 5	1	NM_001188.4	ENSP00000363591.3
BAK1	ENST00000442998.6	c.-32+965A>G		intron_variant	Intron 1 of 6	1		ENSP00000391258.2
GGNBP1	ENST00000612409.1	n.362+3596T>C		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112572 AN: 152052 Hom.: 41769 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.741 AC: 112685 AN: 152170 Hom.: 41826 Cov.: 33 AF XY: 0.746 AC XY: 55508 AN XY: 74404

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.737

Alfa AF: 0.728 Hom.: 44539

Bravo AF: 0.733

Asia WGS AF: 0.833 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.43

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: rs210142; hg19: chr6-33546837;