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GeneBe

22-43127701-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.166G>A(p.Ala56Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,553,504 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 0.000046 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BIK
NM_001197.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06
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=0.026309729).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIKNM_001197.5 linkuse as main transcriptc.166G>A p.Ala56Thr missense_variant 3/5 ENST00000216115.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIKENST00000216115.3 linkuse as main transcriptc.166G>A p.Ala56Thr missense_variant 3/51 NM_001197.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152198
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
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:
0.000478
GnomAD3 exomes
AF:
0.0000189
AC:
3
AN:
158862
Hom.:
0
AF XY:
0.0000237
AC XY:
2
AN XY:
84456
show subpopulations
Gnomad AFR exome
AF:
0.000108
Gnomad AMR exome
AF:
0.00
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:
0.0000322
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000121
AC:
17
AN:
1401306
Hom.:
0
Cov.:
31
AF XY:
0.0000130
AC XY:
9
AN XY:
691616
show subpopulations
Gnomad4 AFR exome
AF:
0.0000940
Gnomad4 AMR exome
AF:
0.0000275
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:
0.00000925
Gnomad4 OTH exome
AF:
0.0000516
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152198
Hom.:
0
Cov.:
34
AF XY:
0.0000538
AC XY:
4
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000392
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:
0.000478
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000128
ExAC
AF:
0.00000892
AC:
1

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 27, 2022The c.166G>A (p.A56T) alteration is located in exon 3 (coding exon 2) of the BIK gene. This alteration results from a G to A substitution at nucleotide position 166, causing the alanine (A) at amino acid position 56 to be replaced by a threonine (T). 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
0.089
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
Cadd
Benign
1.1
Dann
Benign
0.73
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.76
N
REVEL
Benign
0.016
Sift
Benign
0.41
T
Sift4G
Benign
0.44
T
Polyphen
0.10
B
Vest4
0.097
MutPred
0.22
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.11
MPC
0.015
ClinPred
0.013
T
GERP RS
-3.0
Varity_R
0.028
gMVP
0.011

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: rs756641544; hg19: chr22-43523707; COSMIC: COSV99295684; COSMIC: COSV99295684; API