dbSNP rs210135: BAK1:c.*888A>T (chr6-33572915-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001188.4(BAK1):c.*888A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 148,766 control chromosomes in the GnomAD database, including 40,449 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 ( 40404 hom., cov: 24)

Exomes 𝑓: 0.48 ( 45 hom. )

Consequence

BAK1
NM_001188.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.417

Publications

22 publications found

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:

ENSG00000293518 (HGNC:):

ENSG00000293518 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
BAK1	NM_001188.4 link	c.*888A>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000374467.4	NP_001179.1
BAK1	XM_011514779.4 link	c.*888A>T	3_prime_UTR_variant	Exon 7 of 7		XP_011513081.1
BAK1	XM_011514780.2 link	c.*888A>T	3_prime_UTR_variant	Exon 5 of 5		XP_011513082.1
BAK1	XM_047419196.1 link	c.*888A>T	3_prime_UTR_variant	Exon 5 of 5		XP_047275152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4 link	c.*888A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001188.4	ENSP00000363591.3

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

109248

AN:

148440

Hom.:

40345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.830

Gnomad SAS

AF:

0.860

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.721

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.727

GnomAD4 exome

AF:

0.476

AC:

AN:

208

Hom.:

Cov.:

AF XY:

0.453

AC XY:

AN XY:

106

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.601

AC:

AN:

158

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00177336), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.303

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.736

AC:

109363

AN:

148558

Hom.:

40404

Cov.:

AF XY:

0.741

AC XY:

53590

AN XY:

72322

show subpopulations

African (AFR)

AF:

0.727

AC:

29303

AN:

40322

American (AMR)

AF:

0.735

AC:

10963

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.771

AC:

2652

AN:

3438

East Asian (EAS)

AF:

0.830

AC:

4146

AN:

4996

South Asian (SAS)

AF:

0.860

AC:

3911

AN:

4546

European-Finnish (FIN)

AF:

0.788

AC:

8052

AN:

10214

Middle Eastern (MID)

AF:

0.741

AC:

215

AN:

290

European-Non Finnish (NFE)

AF:

0.717

AC:

47975

AN:

66892

Other (OTH)

AF:

0.731

AC:

1489

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

1370

2739

4109

5478

6848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.725

Hom.:

4598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.9

(source)

DANN

Benign

0.79

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over