rs45581936
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001322934.2(NFKB2):c.40G>A(p.Glu14Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000841 in 1,612,586 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00051 ( 3 hom. )
Consequence
NFKB2
NM_001322934.2 missense
NM_001322934.2 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
NFKB2 (HGNC:7795): (nuclear factor kappa B subunit 2) This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NFKB2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006150514).
BP6
?
Variant 10-102396271-G-A is Benign according to our data. Variant chr10-102396271-G-A is described in ClinVar as [Benign]. Clinvar id is 474786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102396271-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00405 (617/152224) while in subpopulation AFR AF= 0.0136 (566/41538). AF 95% confidence interval is 0.0127. There are 4 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 617 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKB2 | NM_001322934.2 | c.40G>A | p.Glu14Lys | missense_variant | 3/23 | ENST00000661543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKB2 | ENST00000661543.1 | c.40G>A | p.Glu14Lys | missense_variant | 3/23 | NM_001322934.2 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.00403 AC: 613AN: 152106Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00119 AC: 298AN: 249404Hom.: 2 AF XY: 0.000902 AC XY: 122AN XY: 135302
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GnomAD4 exome AF: 0.000506 AC: 739AN: 1460362Hom.: 3 Cov.: 33 AF XY: 0.000467 AC XY: 339AN XY: 726134
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GnomAD4 genome ? AF: 0.00405 AC: 617AN: 152224Hom.: 4 Cov.: 31 AF XY: 0.00388 AC XY: 289AN XY: 74420
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ExAC
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168
Asia WGS
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7
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency, common variable, 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 24, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D;.;.
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
Sift4G
Benign
T;D;D;T;D
Polyphen
0.12
.;.;B;.;.
Vest4
0.31, 0.32, 0.31
MVP
MPC
1.4
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at