6-33574761-A-G

Variant names:

• chr6-33574761-A-G
• rs210138
• NM_001188.4:c.350+537T>C

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+537T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,194 control chromosomes in the GnomAD database, including 3,272 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 0.19 (3272 hom., cov: 33)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 73 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAK1	NM_001188.4	c.350+537T>C		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+537T>C		intron_variant	Intron 4 of 5	1	NM_001188.4	ENSP00000363591.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29529 AN: 152076 Hom.: 3253 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.194 AC: 29587 AN: 152194 Hom.: 3272 Cov.: 33 AF XY: 0.197 AC XY: 14691 AN XY: 74408

African (AFR) AF: 0.166 AC: 6911 AN: 41508

American (AMR) AF: 0.210 AC: 3212 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 674 AN: 3462

East Asian (EAS) AF: 0.459 AC: 2373 AN: 5168

South Asian (SAS) AF: 0.370 AC: 1784 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10602

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12600 AN: 68018

Other (OTH) AF: 0.231 AC: 486 AN: 2108

Alfa AF: 0.196 Hom.: 14303

Bravo AF: 0.196

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.43
PhyloP100		-1.3
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: rs210138; hg19: chr6-33542538; COSMIC: COSV62349562;