rs513349

Variant names:

• chr6-33573942-A-G
• rs513349
• NM_001188.4:c.532-35T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-33573942-A-G
• chr6-33573942-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001188.4(BAK1):​c.532-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,490 control chromosomes in the GnomAD database, including 166,392 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.51 (21050 hom., cov: 33)
  • Exomes 𝑓: 0.43 (145342 hom.)
• Consequence: BAK1 NM_001188.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842
• Publications: 42 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 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.532-35T>C		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.532-35T>C		intron	N/A	ENSP00000363591.3	Q16611-1
	BAK1	ENST00000442998.6	TSL:1	c.*90-35T>C		intron	N/A	ENSP00000391258.2	Q16611-2
	BAK1	ENST00000938018.1		c.709-35T>C		intron	N/A	ENSP00000608077.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77519 AN: 152008 Hom.: 20998 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.513

GnomAD2 exomes AF: 0.513 AC: 128446 AN: 250428 AF XY: 0.520

Gnomad AFR exome AF: 0.653

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.794

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.432 AC: 630678 AN: 1461364 Hom.: 145342 Cov.: 36 AF XY: 0.441 AC XY: 320802 AN XY: 726998

African (AFR) AF: 0.663 AC: 22200 AN: 33478

American (AMR) AF: 0.514 AC: 22943 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12864 AN: 26136

East Asian (EAS) AF: 0.717 AC: 28450 AN: 39682

South Asian (SAS) AF: 0.734 AC: 63294 AN: 86246

European-Finnish (FIN) AF: 0.426 AC: 22772 AN: 53406

Middle Eastern (MID) AF: 0.512 AC: 2949 AN: 5764

European-Non Finnish (NFE) AF: 0.384 AC: 427246 AN: 1111600

Other (OTH) AF: 0.463 AC: 27960 AN: 60378

GnomAD4 genome AF: 0.510 AC: 77631 AN: 152126 Hom.: 21050 Cov.: 33 AF XY: 0.520 AC XY: 38694 AN XY: 74372

African (AFR) AF: 0.647 AC: 26862 AN: 41508

American (AMR) AF: 0.525 AC: 8033 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3968 AN: 5160

South Asian (SAS) AF: 0.745 AC: 3588 AN: 4818

European-Finnish (FIN) AF: 0.431 AC: 4564 AN: 10582

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27111 AN: 67976

Other (OTH) AF: 0.519 AC: 1097 AN: 2114

Alfa AF: 0.439 Hom.: 67664

Bravo AF: 0.517

Asia WGS AF: 0.723 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.39
PhyloP100		0.84
BranchPoint Hunter		2.0
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: rs513349; hg19: chr6-33541719; COSMIC: COSV62349614;