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GeneBe

22-43128615-C-T

Variant summary

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

The NM_001197.5(BIK):c.380C>T(p.Pro127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,610,416 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 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

BIK
NM_001197.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.261
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=0.050059915).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIKNM_001197.5 linkuse as main transcriptc.380C>T p.Pro127Leu missense_variant 4/5 ENST00000216115.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIKENST00000216115.3 linkuse as main transcriptc.380C>T p.Pro127Leu missense_variant 4/51 NM_001197.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248724
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134468
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS 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:
0.00000754
AC:
11
AN:
1458180
Hom.:
0
Cov.:
34
AF XY:
0.00000414
AC XY:
3
AN XY:
725116
show subpopulations
Gnomad4 AFR exome
AF:
0.0000899
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000996
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
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 GeneticsOct 12, 2021The c.380C>T (p.P127L) alteration is located in exon 4 (coding exon 3) of the BIK gene. This alteration results from a C to T substitution at nucleotide position 380, causing the proline (P) at amino acid position 127 to be replaced by a leucine (L). 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
0.13
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.69
Cadd
Benign
1.8
Dann
Benign
0.94
DEOGEN2
Benign
0.20
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.050
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-4.1
D
REVEL
Benign
0.027
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.011
D
Polyphen
0.0040
B
Vest4
0.051
MVP
0.27
MPC
0.015
ClinPred
0.053
T
GERP RS
-2.5
Varity_R
0.075
gMVP
0.016

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

LitVar

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

Other links and lift over

dbSNP: rs368572843; hg19: chr22-43524621; API