rs11757379

chr6-33574884-G-T

Variant summary

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

The NM_001188.4(BAK1):c.350+414C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,214 control chromosomes in the GnomAD database, including 2,837 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 0.16 (2837 hom., cov: 32)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAK1	NM_001188.4	c.350+414C>A		intron_variant		ENST00000374467.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAK1	ENST00000374467.4	c.350+414C>A		intron_variant		1	NM_001188.4	P1
BAK1	ENST00000442998.6	c.351-359C>A		intron_variant		1
GGNBP1	ENST00000612409.1	n.249-467G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24775 AN: 152096 Hom.: 2836 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.163 AC: 24778 AN: 152214 Hom.: 2837 Cov.: 32 AF XY: 0.161 AC XY: 12013 AN XY: 74424

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.161

Alfa AF: 0.181 Hom.: 611

Bravo AF: 0.147

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.85

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: rs11757379; hg19: chr6-33542661;