6-31557780-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005007.4(NFKBIL1):ā€‹c.487C>Gā€‹(p.Arg163Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.155
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 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=0.051853716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.487C>G p.Arg163Gly missense_variant 3/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.487C>G p.Arg163Gly missense_variant 3/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.418C>G p.Arg140Gly missense_variant 3/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.418C>G p.Arg140Gly 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.487C>G p.Arg163Gly missense_variant 3/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.487C>G p.Arg163Gly missense_variant 3/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.418C>G p.Arg140Gly missense_variant 3/44 ENSP00000365316 A1Q9UBC1-2
NFKBIL1ENST00000473655.1 linkuse as main transcriptn.521C>G non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460090
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726134
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 GeneticsDec 16, 2023The c.487C>G (p.R163G) alteration is located in exon 3 (coding exon 3) of the NFKBIL1 gene. This alteration results from a C to G substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 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
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Uncertain
0.97
DEOGEN2
Benign
0.034
T;.;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.73
T;.;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.052
T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Benign
0.056
Sift
Benign
0.046
D;D;T
Sift4G
Benign
0.10
T;T;T
Polyphen
0.011
B;.;.
Vest4
0.22
MutPred
0.34
.;Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP
0.10
MPC
1.1
ClinPred
0.11
T
GERP RS
2.5
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: chr6-31525557; API