chr6-31558279-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005007.4(NFKBIL1):ā€‹c.814C>Gā€‹(p.Arg272Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,586,526 control chromosomes in the GnomAD database, including 5 homozygotes. 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 Likely benign (no stars).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 31)
Exomes š‘“: 0.00043 ( 5 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

18

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0210
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002812922).
BP6
Variant 6-31558279-C-G is Benign according to our data. Variant chr6-31558279-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3058781.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.814C>G p.Arg272Gly missense_variant 4/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.769C>G p.Arg257Gly missense_variant 4/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.745C>G p.Arg249Gly missense_variant 4/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.700C>G p.Arg234Gly 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.814C>G p.Arg272Gly missense_variant 4/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.769C>G p.Arg257Gly missense_variant 4/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.745C>G p.Arg249Gly missense_variant 4/44 ENSP00000365316 A1Q9UBC1-2

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152122
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:
0.00
Gnomad SAS
AF:
0.00498
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000989
AC:
201
AN:
203138
Hom.:
3
AF XY:
0.00141
AC XY:
156
AN XY:
110946
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:
0.00730
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000567
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000427
AC:
613
AN:
1434286
Hom.:
5
Cov.:
35
AF XY:
0.000636
AC XY:
452
AN XY:
710598
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00675
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000300
Gnomad4 OTH exome
AF:
0.000253
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152240
Hom.:
0
Cov.:
31
AF XY:
0.000309
AC XY:
23
AN XY:
74430
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:
0.00498
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000157
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.000942
AC:
110
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

ClinVar

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

Submissions by phenotype

NFKBIL1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesApr 04, 2019This variant is classified as likely 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
0.059
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
4.4
DANN
Benign
0.92
DEOGEN2
Benign
0.0072
T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.57
T;.;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.0028
T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.017
Sift
Benign
0.16
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.011
B;.;.
Vest4
0.051
MVP
0.093
MPC
0.78
ClinPred
0.0091
T
GERP RS
2.8
gMVP
0.40

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: rs200733771; hg19: chr6-31526056; API