rs146926941
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001322934.2(NFKB2):c.921G>A(p.Leu307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,614,186 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 1 hom. )
Consequence
NFKB2
NM_001322934.2 synonymous
NM_001322934.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.49
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 10-102398453-G-A is Benign according to our data. Variant chr10-102398453-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102398453-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.49 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000611 (93/152304) while in subpopulation NFE AF= 0.00107 (73/68036). AF 95% confidence interval is 0.000875. There are 1 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 94 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKB2 | NM_001322934.2 | c.921G>A | p.Leu307= | synonymous_variant | 11/23 | ENST00000661543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKB2 | ENST00000661543.1 | c.921G>A | p.Leu307= | synonymous_variant | 11/23 | NM_001322934.2 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152186Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000517 AC: 129AN: 249550Hom.: 0 AF XY: 0.000495 AC XY: 67AN XY: 135386
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GnomAD4 exome AF: 0.000568 AC: 830AN: 1461882Hom.: 1 Cov.: 34 AF XY: 0.000575 AC XY: 418AN XY: 727244
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GnomAD4 genome ? AF: 0.000611 AC: 93AN: 152304Hom.: 1 Cov.: 32 AF XY: 0.000618 AC XY: 46AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | NFKB2: BP4, BP7 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Immunodeficiency, common variable, 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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