6-31558301-C-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.836C>Gā€‹(p.Ala279Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,580,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 31)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
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=0.08887783).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.836C>G p.Ala279Gly missense_variant 4/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.791C>G p.Ala264Gly missense_variant 4/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.767C>G p.Ala256Gly missense_variant 4/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.722C>G p.Ala241Gly missense_variant 4/4 NP_001138435.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFKBIL1ENST00000376148.9 linkuse as main transcriptc.836C>G p.Ala279Gly missense_variant 4/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.791C>G p.Ala264Gly missense_variant 4/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.767C>G p.Ala256Gly missense_variant 4/44 ENSP00000365316 A1Q9UBC1-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
31
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:
0.000193
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
GnomAD4 exome
AF:
7.00e-7
AC:
1
AN:
1428218
Hom.:
0
Cov.:
35
AF XY:
0.00000141
AC XY:
1
AN XY:
706890
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:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 23, 2023The c.836C>G (p.A279G) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a C to G substitution at nucleotide position 836, causing the alanine (A) at amino acid position 279 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
0.070
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0097
T;.;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.76
T;.;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.75
N;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.52
N;N;N
REVEL
Benign
0.089
Sift
Benign
0.48
T;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.68
P;.;.
Vest4
0.22
MutPred
0.20
.;Gain of methylation at R278 (P = 0.0857);.;
MVP
0.45
MPC
0.78
ClinPred
0.32
T
GERP RS
4.8
gMVP
0.34

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: rs1461793520; hg19: chr6-31526078; API