Variant chr6-33573942-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.842

Variant links:

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]

BAK1 links:

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]

GGNBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BAK1	NM_001188.4 linkuse as main transcript	c.532-35T>C	intron_variant	ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4 linkuse as main transcript	c.532-35T>C	intron_variant		XP_011513081.1
BAK1	XM_011514780.2 linkuse as main transcript	c.355-35T>C	intron_variant		XP_011513082.1
BAK1	XM_047419196.1 linkuse as main transcript	c.355-35T>C	intron_variant		XP_047275152.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4 linkuse as main transcript	c.532-35T>C	intron_variant	1	NM_001188.4	ENSP00000363591	P1	Q16611-1
BAK1	ENST00000442998.6 linkuse as main transcript	c.*90-35T>C	intron_variant	1		ENSP00000391258		Q16611-2
GGNBP1	ENST00000612409.1 linkuse as main transcript	n.249-1409A>G	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77519

AN:

152008

Hom.:

20998

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.513

AC:

128446

AN:

250428

Hom.:

35436

AF XY:

0.520

AC XY:

70395

AN XY:

135388

show subpopulations

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 SAS exome

AF:

0.736

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.:

AF XY:

0.441

AC XY:

320802

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.492

Gnomad4 EAS exome

AF:

0.717

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.463

GnomAD4 genome

AF:

0.510

AC:

77631

AN:

152126

Hom.:

21050

Cov.:

AF XY:

0.520

AC XY:

38694

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.745

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.429

Hom.:

28365

Bravo

AF:

0.517

Asia WGS

AF:

0.723

AC:

2515

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

5.9

DANN

Benign

0.39

BranchPoint Hunter

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over