chr4-102510933-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_003998.4(NFKB1):c.-8+9145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,285,530 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0049 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0078 ( 47 hom. )
Consequence
NFKB1
NM_003998.4 intron
NM_003998.4 intron
Scores
1
1
11
Clinical Significance
Conservation
PhyloP100: 0.405
Genes affected
NFKB1 (HGNC:7794): (nuclear factor kappa B subunit 1) This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. NFKB is a critical regulator of the immediate-early response to viral infection. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006662905).
BP6
?
Variant 4-102510933-A-G is Benign according to our data. Variant chr4-102510933-A-G is described in ClinVar as [Benign]. Clinvar id is 1675952.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00489 (744/152282) while in subpopulation NFE AF= 0.00853 (580/68030). AF 95% confidence interval is 0.00795. There are 3 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 744 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFKB1 | NM_003998.4 | c.-8+9145A>G | intron_variant | ENST00000226574.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFKB1 | ENST00000226574.9 | c.-8+9145A>G | intron_variant | 1 | NM_003998.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00489 AC: 744AN: 152164Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00400 AC: 509AN: 127208Hom.: 1 AF XY: 0.00396 AC XY: 276AN XY: 69774
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GnomAD4 exome AF: 0.00778 AC: 8817AN: 1133248Hom.: 47 Cov.: 29 AF XY: 0.00757 AC XY: 4207AN XY: 556046
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GnomAD4 genome ? AF: 0.00489 AC: 744AN: 152282Hom.: 3 Cov.: 32 AF XY: 0.00465 AC XY: 346AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | NFKB1: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
MVP
ClinPred
T
GERP RS
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