Genetic Variant BOK:p.Glu155Val (chr2-241570239-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_032515.5(BOK):c.464A>T(p.Glu155Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,592,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

BOK
NM_032515.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.58

Publications

0 publications found

Variant links:

Genes affected

BOK (HGNC:1087): (BCL2 family apoptosis regulator BOK) The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes. Studies in rat show that this protein has restricted expression in reproductive tissues, interacts strongly with some antiapoptotic BCL2 proteins, not at all with proapoptotic BCL2 proteins, and induces apoptosis in transfected cells. Thus, this protein represents a proapoptotic member of the BCL2 family. [provided by RefSeq, Sep 2011]

BOK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032515.5. 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
	BOK	NM_032515.5	MANE Select	c.464A>T	p.Glu155Val	missense	Exon 4 of 5	NP_115904.1	A0A024R4A8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BOK	ENST00000318407.5	TSL:1 MANE Select	c.464A>T	p.Glu155Val	missense	Exon 4 of 5	ENSP00000314132.3	Q9UMX3-1
BOK	ENST00000853586.1		c.563A>T	p.Glu188Val	missense	Exon 4 of 5	ENSP00000523645.1
BOK	ENST00000969136.1		c.563A>T	p.Glu188Val	missense	Exon 5 of 6	ENSP00000639195.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000712

AC:

AN:

210768

AF XY:

0.0000524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000507

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1440654

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

715516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32898

American (AMR)

AF:

0.000488

AC:

AN:

40982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25710

East Asian (EAS)

AF:

0.00

AC:

AN:

38488

South Asian (SAS)

AF:

0.00

AC:

AN:

83866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4822

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103266

Other (OTH)

AF:

0.00

AC:

AN:

59528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

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:

0.0000263

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41314

American (AMR)

AF:

0.000262

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000250

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.1

PhyloP100

8.6

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.47

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.94

Vest4

0.92

MutPred

0.56

Gain of catalytic residue at E155 (P = 0.0256)

MVP

0.82

MPC

0.58

ClinPred

0.54

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.74

Mutation Taster

=39/61

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over