chr6-31557636-G-A

Variant summary

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

The NM_005007.4(NFKBIL1):​c.343G>A​(p.Asp115Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000152 in 1,529,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56
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 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=0.18557781).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.343G>A p.Asp115Asn missense_variant 3/4 ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcriptc.343G>A p.Asp115Asn missense_variant 3/4 NP_001138433.1
NFKBIL1NM_001144962.2 linkuse as main transcriptc.274G>A p.Asp92Asn missense_variant 3/4 NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.274G>A p.Asp92Asn 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.343G>A p.Asp115Asn missense_variant 3/41 NM_005007.4 ENSP00000365318 P4Q9UBC1-1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000129
AC:
26
AN:
201462
Hom.:
0
AF XY:
0.000102
AC XY:
11
AN XY:
107994
show subpopulations
Gnomad AFR exome
AF:
0.0000645
Gnomad AMR exome
AF:
0.0000760
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000142
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000205
Gnomad OTH exome
AF:
0.000215
GnomAD4 exome
AF:
0.000154
AC:
212
AN:
1377430
Hom.:
0
Cov.:
31
AF XY:
0.000160
AC XY:
108
AN XY:
675344
show subpopulations
Gnomad4 AFR exome
AF:
0.0000641
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000411
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000183
Gnomad4 OTH exome
AF:
0.000106
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000217
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000115
AC:
14

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 GeneticsFeb 16, 2023The c.343G>A (p.D115N) alteration is located in exon 3 (coding exon 3) of the NFKBIL1 gene. This alteration results from a G to A substitution at nucleotide position 343, causing the aspartic acid (D) at amino acid position 115 to be replaced by an asparagine (N). 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
Uncertain
0.34
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T;.;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;.;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.5
N;N;N
REVEL
Benign
0.23
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.14
T;T;T
Polyphen
0.91
P;.;.
Vest4
0.26
MVP
0.46
MPC
1.2
ClinPred
0.11
T
GERP RS
5.9
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200454925; hg19: chr6-31525413; API