6-31558217-G-A

Variant summary

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

The NM_005007.4(NFKBIL1):​c.752G>A​(p.Arg251Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,597,688 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 6 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
16

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.509
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=0.0024567246).
BP6
Variant 6-31558217-G-A is Benign according to our data. Variant chr6-31558217-G-A is described in ClinVar as [Benign]. Clinvar id is 3034111.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.752G>A p.Arg251Gln missense_variant 4/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.707G>A p.Arg236Gln missense_variant 4/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.683G>A p.Arg228Gln missense_variant 4/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.638G>A p.Arg213Gln 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.752G>A p.Arg251Gln missense_variant 4/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcriptc.707G>A p.Arg236Gln missense_variant 4/41 ENSP00000365315 Q9UBC1-3
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.683G>A p.Arg228Gln missense_variant 4/44 ENSP00000365316 A1Q9UBC1-2

Frequencies

GnomAD3 genomes
AF:
0.00220
AC:
335
AN:
152230
Hom.:
6
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0253
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000603
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00228
AC:
479
AN:
210474
Hom.:
4
AF XY:
0.00221
AC XY:
254
AN XY:
115086
show subpopulations
Gnomad AFR exome
AF:
0.000251
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0220
Gnomad NFE exome
AF:
0.000589
Gnomad OTH exome
AF:
0.000745
GnomAD4 exome
AF:
0.00112
AC:
1618
AN:
1445340
Hom.:
10
Cov.:
35
AF XY:
0.00105
AC XY:
755
AN XY:
717308
show subpopulations
Gnomad4 AFR exome
AF:
0.000330
Gnomad4 AMR exome
AF:
0.000241
Gnomad4 ASJ exome
AF:
0.0000389
Gnomad4 EAS exome
AF:
0.0000765
Gnomad4 SAS exome
AF:
0.0000476
Gnomad4 FIN exome
AF:
0.0190
Gnomad4 NFE exome
AF:
0.000515
Gnomad4 OTH exome
AF:
0.000835
GnomAD4 genome
AF:
0.00220
AC:
335
AN:
152348
Hom.:
6
Cov.:
31
AF XY:
0.00305
AC XY:
227
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000481
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0253
Gnomad4 NFE
AF:
0.000603
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000618
Hom.:
0
Bravo
AF:
0.000340
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000332
AC:
1
ESP6500EA
AF:
0.000370
AC:
2
ExAC
AF:
0.00171
AC:
201

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 SciencesJun 11, 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
0.083
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T;.;T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.74
T;.;T
MetaRNN
Benign
0.0025
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.89
N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.044
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.0060
B;.;.
Vest4
0.060
MVP
0.26
MPC
0.71
ClinPred
0.015
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.35

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: rs149963082; hg19: chr6-31525994; API