6-31558344-C-G

Variant summary

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

The NM_005007.4(NFKBIL1):​c.879C>G​(p.Ser293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 31)

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.529
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]

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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=0.06978181).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.879C>G p.Ser293Arg missense_variant 4/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.834C>G p.Ser278Arg missense_variant 4/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.810C>G p.Ser270Arg missense_variant 4/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.765C>G p.Ser255Arg 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.879C>G p.Ser293Arg missense_variant 4/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.834C>G p.Ser278Arg missense_variant 4/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.810C>G p.Ser270Arg missense_variant 4/44 ENSP00000365316 A1Q9UBC1-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
31

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 GeneticsJun 13, 2024The c.879C>G (p.S293R) 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 879, causing the serine (S) at amino acid position 293 to be replaced by an arginine (R). 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
0.15
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
12
DANN
Benign
0.97
DEOGEN2
Benign
0.0090
T;.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.64
T;.;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.070
T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
0.78
N;N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.46
N;N;N
REVEL
Benign
0.059
Sift
Benign
0.39
T;T;T
Sift4G
Benign
0.45
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.10
MutPred
0.36
.;Loss of phosphorylation at S293 (P = 0.0115);.;
MVP
0.12
MPC
0.69
ClinPred
0.21
T
GERP RS
-0.99
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31526121; API