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GeneBe

22-43129222-G-A

Variant summary

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

The NM_001197.5(BIK):c.400G>A(p.Glu134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000517 in 1,604,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

BIK
NM_001197.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.45
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]

Genome browser will be placed here

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=0.010476798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIKNM_001197.5 linkuse as main transcriptc.400G>A p.Glu134Lys missense_variant 5/5 ENST00000216115.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIKENST00000216115.3 linkuse as main transcriptc.400G>A p.Glu134Lys missense_variant 5/51 NM_001197.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152042
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000969
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000129
AC:
31
AN:
240912
Hom.:
0
AF XY:
0.000114
AC XY:
15
AN XY:
131832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000989
Gnomad SAS exome
AF:
0.000197
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000441
AC:
64
AN:
1452552
Hom.:
0
Cov.:
35
AF XY:
0.0000553
AC XY:
40
AN XY:
722952
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000454
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000971
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000754
Hom.:
0
Bravo
AF:
0.000106
ExAC
AF:
0.000132
AC:
16
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsMay 03, 2023The c.400G>A (p.E134K) alteration is located in exon 5 (coding exon 4) of the BIK gene. This alteration results from a G to A substitution at nucleotide position 400, causing the glutamic acid (E) at amino acid position 134 to be replaced by a lysine (K). 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
0.10
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
0.030
Dann
Benign
0.78
DEOGEN2
Benign
0.060
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.060
N
REVEL
Benign
0.0070
Sift
Benign
0.38
T
Sift4G
Benign
0.66
T
Polyphen
0.013
B
Vest4
0.092
MutPred
0.45
Gain of methylation at E134 (P = 0.0014);
MVP
0.14
MPC
0.013
ClinPred
0.028
T
GERP RS
-8.5
Varity_R
0.031
gMVP
0.031

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: rs532663391; hg19: chr22-43525228; COSMIC: COSV51792892; COSMIC: COSV51792892; API