Genetic Variant NM_032515.5:c.167C>T (chr2-241559650-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032515.5(BOK):c.167C>T(p.Ala56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,239,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A56G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

BOK
NM_032515.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09409961).

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.167C>T	p.Ala56Val	missense	Exon 2 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.167C>T	p.Ala56Val	missense	Exon 2 of 5	ENSP00000314132.3	Q9UMX3-1
BOK	ENST00000853586.1		c.167C>T	p.Ala56Val	missense	Exon 1 of 5	ENSP00000523645.1
BOK	ENST00000969136.1		c.167C>T	p.Ala56Val	missense	Exon 2 of 6	ENSP00000639195.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.07e-7

AC:

AN:

1239404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

606392

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:

24388

American (AMR)

AF:

0.00

AC:

AN:

12976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18068

East Asian (EAS)

AF:

0.00

AC:

AN:

27822

South Asian (SAS)

AF:

0.00

AC:

AN:

56936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4540

European-Non Finnish (NFE)

AF:

9.87e-7

AC:

AN:

1013518

Other (OTH)

AF:

0.00

AC:

AN:

50936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.67

M_CAP

Benign

0.050

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.040

REVEL

Benign

0.012

Sift

Benign

0.36

Sift4G

Benign

0.41

Polyphen

0.040

Vest4

0.14

MutPred

0.29

Loss of disorder (P = 0.0662)

MVP

0.22

MPC

1.3

ClinPred

0.067

GERP RS

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.27

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over