6-33579060-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001188.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAK1	NM_001188.4	MANE Select	c.-32+965A>G		intron	N/A	NP_001179.1	Q16611-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAK1	ENST00000374467.4	TSL:1 MANE Select	c.-32+965A>G		intron	N/A	ENSP00000363591.3	Q16611-1
	BAK1	ENST00000442998.6	TSL:1	c.-32+965A>G		intron	N/A	ENSP00000391258.2	Q16611-2
	BAK1	ENST00000886798.1		c.-1456A>G		5_prime_UTR	Exon 1 of 5	ENSP00000556857.1

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

African (AFR) AF: 0.735 AC: 30528 AN: 41518

American (AMR) AF: 0.739 AC: 11304 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2677 AN: 3470

East Asian (EAS) AF: 0.834 AC: 4309 AN: 5166

South Asian (SAS) AF: 0.864 AC: 4169 AN: 4828

European-Finnish (FIN) AF: 0.795 AC: 8427 AN: 10594

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48828 AN: 67974

Other (OTH) AF: 0.737 AC: 1559 AN: 2116

Alfa AF: 0.729 Hom.: 63964

Bravo AF: 0.733

Asia WGS AF: 0.833 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.43
PhyloP100		-1.7
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: rs210142; hg19: chr6-33546837;