Genetic Variant NM_001197.5:c.445C>T (chr22-43129267-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001197.5(BIK):c.445C>T(p.Pro149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. P149A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BIK
NM_001197.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.673

Publications

2 publications found

Variant links:

Genes affected

BIK (HGNC:1051): (BCL2 interacting killer) The protein encoded by this gene shares a critical BH3 domain with other death-promoting proteins, such as BID, BAK, BAD and BAX, that is required for its pro-apoptotic activity, and for interaction with anti-apoptotic members of the BCL2 family, and viral survival-promoting proteins. Since the activity of this protein is suppressed in the presence of survival-promoting proteins, it is suggested as a likely target for anti-apoptotic proteins. [provided by RefSeq, Sep 2011]

BIK Gene-Disease associations (from GenCC):

prostate cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BIK links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037914217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197.5. 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
	BIK	NM_001197.5	MANE Select	c.445C>T	p.Pro149Ser	missense	Exon 5 of 5	NP_001188.1	Q13323

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIK	ENST00000216115.3	TSL:1 MANE Select	c.445C>T	p.Pro149Ser	missense	Exon 5 of 5	ENSP00000216115.2	Q13323
BIK	ENST00000918052.1		c.559C>T	p.Pro187Ser	missense	Exon 6 of 6	ENSP00000588111.1
BIK	ENST00000910665.1		c.445C>T	p.Pro149Ser	missense	Exon 7 of 7	ENSP00000580724.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720680

African (AFR)

AF:

0.00

AC:

AN:

33318

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109502

Other (OTH)

AF:

0.00

AC:

AN:

60168

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.79

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.062

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.30

M_CAP

Benign

0.0050

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-0.67

PrimateAI

Benign

0.30

PROVEAN

Benign

0.50

REVEL

Benign

0.0080

Sift

Pathogenic

0.0

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.064

MutPred

0.26

Gain of helix (P = 0.062)

MVP

0.12

MPC

0.016

ClinPred

0.068

GERP RS

-4.1

Varity_R

0.045

gMVP

0.027

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over