6-31557683-A-G

Variant summary

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

The NM_005007.4(NFKBIL1):ā€‹c.390A>Gā€‹(p.Ile130Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,585,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.568
Variant links:
Genes affected
NFKBIL1 (HGNC:7800): (NFKB inhibitor like 1) This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

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=0.14051107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.390A>G p.Ile130Met missense_variant 3/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.390A>G p.Ile130Met missense_variant 3/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.321A>G p.Ile107Met missense_variant 3/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.321A>G p.Ile107Met missense_variant 3/4 NP_001138435.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFKBIL1ENST00000376148.9 linkuse as main transcriptc.390A>G p.Ile130Met missense_variant 3/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
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:
0.00000416
AC:
1
AN:
240500
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130390
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000914
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1433458
Hom.:
0
Cov.:
33
AF XY:
0.00000141
AC XY:
1
AN XY:
709116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74370
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
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 GeneticsAug 22, 2023The c.390A>G (p.I130M) alteration is located in exon 3 (coding exon 3) of the NFKBIL1 gene. This alteration results from a A to G substitution at nucleotide position 390, causing the isoleucine (I) at amino acid position 130 to be replaced by a methionine (M). 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
0.16
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
17
DANN
Benign
0.84
DEOGEN2
Benign
0.012
T;.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.72
T;.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.90
D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
0.24
N;N;N
REVEL
Benign
0.078
Sift
Benign
0.19
T;T;T
Sift4G
Benign
0.47
T;T;T
Polyphen
0.0030
B;.;.
Vest4
0.22
MutPred
0.49
.;Gain of catalytic residue at I130 (P = 0.0071);Gain of catalytic residue at I130 (P = 0.0071);
MVP
0.49
MPC
0.71
ClinPred
0.14
T
GERP RS
2.3
gMVP
0.35

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: rs756356865; hg19: chr6-31525460; API