6-31558135-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005007.4(NFKBIL1):​c.670C>T​(p.Arg224Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,611,914 control chromosomes in the GnomAD database, including 702,866 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.95 ( 69357 hom., cov: 31)
Exomes 𝑓: 0.93 ( 633509 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

17

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.01
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 Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=7.35233E-7).
BP6
Variant 6-31558135-C-T is Benign according to our data. Variant chr6-31558135-C-T is described in ClinVar as [Benign]. Clinvar id is 3060091.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.670C>T p.Arg224Cys missense_variant 4/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.625C>T p.Arg209Cys missense_variant 4/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.601C>T p.Arg201Cys missense_variant 4/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.556C>T p.Arg186Cys 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.670C>T p.Arg224Cys missense_variant 4/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.625C>T p.Arg209Cys missense_variant 4/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.601C>T p.Arg201Cys missense_variant 4/44 ENSP00000365316 A1Q9UBC1-2

Frequencies

GnomAD3 genomes
AF:
0.954
AC:
145111
AN:
152130
Hom.:
69294
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.986
Gnomad AMI
AF:
0.975
Gnomad AMR
AF:
0.967
Gnomad ASJ
AF:
0.992
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
1.00
Gnomad FIN
AF:
0.922
Gnomad MID
AF:
1.00
Gnomad NFE
AF:
0.927
Gnomad OTH
AF:
0.971
GnomAD3 exomes
AF:
0.955
AC:
231948
AN:
242782
Hom.:
110974
AF XY:
0.956
AC XY:
127023
AN XY:
132808
show subpopulations
Gnomad AFR exome
AF:
0.987
Gnomad AMR exome
AF:
0.976
Gnomad ASJ exome
AF:
0.993
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
0.999
Gnomad FIN exome
AF:
0.917
Gnomad NFE exome
AF:
0.929
Gnomad OTH exome
AF:
0.953
GnomAD4 exome
AF:
0.931
AC:
1359001
AN:
1459666
Hom.:
633509
Cov.:
76
AF XY:
0.934
AC XY:
677948
AN XY:
726054
show subpopulations
Gnomad4 AFR exome
AF:
0.988
Gnomad4 AMR exome
AF:
0.976
Gnomad4 ASJ exome
AF:
0.993
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.999
Gnomad4 FIN exome
AF:
0.919
Gnomad4 NFE exome
AF:
0.918
Gnomad4 OTH exome
AF:
0.942
GnomAD4 genome
AF:
0.954
AC:
145233
AN:
152248
Hom.:
69357
Cov.:
31
AF XY:
0.955
AC XY:
71064
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.986
Gnomad4 AMR
AF:
0.967
Gnomad4 ASJ
AF:
0.992
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
1.00
Gnomad4 FIN
AF:
0.922
Gnomad4 NFE
AF:
0.927
Gnomad4 OTH
AF:
0.972
Alfa
AF:
0.937
Hom.:
109995
Bravo
AF:
0.959
TwinsUK
AF:
0.918
AC:
3404
ALSPAC
AF:
0.917
AC:
3534
ESP6500AA
AF:
0.983
AC:
2966
ESP6500EA
AF:
0.929
AC:
5035
ExAC
AF:
0.955
AC:
112326
Asia WGS
AF:
0.996
AC:
3465
AN:
3478
EpiCase
AF:
0.940
EpiControl
AF:
0.942

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NFKBIL1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.39
DANN
Benign
0.86
DEOGEN2
Benign
0.022
T;.;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.20
T;.;T
MetaRNN
Benign
7.4e-7
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.5
N;N;N
REVEL
Benign
0.090
Sift
Benign
0.18
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.041
MPC
0.83
ClinPred
0.0080
T
GERP RS
-8.9
gMVP
0.22

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: rs3130062; hg19: chr6-31525912; API