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GeneBe

22-43128525-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001197.5(BIK):c.290C>G(p.Thr97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

BIK
NM_001197.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.508
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.062192917).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIKNM_001197.5 linkuse as main transcriptc.290C>G p.Thr97Ser missense_variant 4/5 ENST00000216115.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIKENST00000216115.3 linkuse as main transcriptc.290C>G p.Thr97Ser missense_variant 4/51 NM_001197.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000147
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251432
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461558
Hom.:
0
Cov.:
34
AF XY:
0.0000811
AC XY:
59
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000944
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000957
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.0000907
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2021The c.290C>G (p.T97S) alteration is located in exon 4 (coding exon 3) of the BIK gene. This alteration results from a C to G substitution at nucleotide position 290, causing the threonine (T) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.75
Cadd
Benign
2.2
Dann
Benign
0.62
DEOGEN2
Benign
0.21
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.90
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.0090
Sift
Benign
0.089
T
Sift4G
Benign
0.067
T
Polyphen
0.16
B
Vest4
0.16
MutPred
0.24
Loss of helix (P = 0.028);
MVP
0.18
MPC
0.015
ClinPred
0.068
T
GERP RS
-3.6
Varity_R
0.058
gMVP
0.029

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

LitVar

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

Other links and lift over

dbSNP: rs777319617; hg19: chr22-43524531; API