rs11757379

Variant names:

• chr6-33574884-G-T
• rs11757379
• NM_001188.4:c.350+414C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ENSG00000293518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BAK1	NM_001188.4	c.350+414C>A		intron_variant	Intron 4 of 5	ENST00000374467.4	NP_001179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.350+414C>A		intron_variant	Intron 4 of 5	1	NM_001188.4	ENSP00000363591.3

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

African (AFR) AF: 0.0388 AC: 1611 AN: 41552

American (AMR) AF: 0.148 AC: 2262 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3466

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5190

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4826

European-Finnish (FIN) AF: 0.307 AC: 3255 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16042 AN: 67982

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.176 Hom.: 1104

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
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11757379; hg19: chr6-33542661;