1-151042967-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138278.4(BNIPL):​c.445C>G​(p.Arg149Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 1,579,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

BNIPL
NM_138278.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.378
Variant links:
Genes affected
BNIPL (HGNC:16976): (BCL2 interacting protein like) The protein encoded by this gene interacts with several other proteins, such as BCL2, ARHGAP1, MIF and GFER. It may function as a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0897598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BNIPLNM_138278.4 linkc.445C>G p.Arg149Gly missense_variant Exon 5 of 10 ENST00000368931.8 NP_612122.2 Q7Z465-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BNIPLENST00000368931.8 linkc.445C>G p.Arg149Gly missense_variant Exon 5 of 10 1 NM_138278.4 ENSP00000357927.3 Q7Z465-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000454
AC:
1
AN:
220502
Hom.:
0
AF XY:
0.00000834
AC XY:
1
AN XY:
119906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000407
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000420
AC:
6
AN:
1427260
Hom.:
0
Cov.:
31
AF XY:
0.00000564
AC XY:
4
AN XY:
709420
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000295
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:
0.00000454
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152052
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
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
Dec 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.445C>G (p.R149G) alteration is located in exon 5 (coding exon 5) of the BNIPL gene. This alteration results from a C to G substitution at nucleotide position 445, causing the arginine (R) at amino acid position 149 to be replaced by a glycine (G). 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
0.077
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0036
.;T;.;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.72
.;T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.090
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;L;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.17
.;N;N;N
REVEL
Benign
0.055
Sift
Benign
0.27
.;T;T;D
Sift4G
Benign
0.17
.;T;T;D
Polyphen
0.39
.;B;.;.
Vest4
0.31, 0.29
MutPred
0.23
.;Gain of sheet (P = 0.1208);.;.;
MVP
0.60
MPC
0.65
ClinPred
0.22
T
GERP RS
4.7
Varity_R
0.094
gMVP
0.22

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: rs151319763; hg19: chr1-151015443; API