rs230520

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003998.4(NFKB1):​c.258+6499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,036 control chromosomes in the GnomAD database, including 41,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 41716 hom., cov: 31)

Consequence

NFKB1
NM_003998.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.529
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NFKB1NM_003998.4 linkuse as main transcriptc.258+6499G>A intron_variant ENST00000226574.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFKB1ENST00000226574.9 linkuse as main transcriptc.258+6499G>A intron_variant 1 NM_003998.4 P4P19838-2

Frequencies

GnomAD3 genomes
AF:
0.729
AC:
110673
AN:
151918
Hom.:
41650
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.922
Gnomad AMI
AF:
0.705
Gnomad AMR
AF:
0.593
Gnomad ASJ
AF:
0.685
Gnomad EAS
AF:
0.576
Gnomad SAS
AF:
0.744
Gnomad FIN
AF:
0.629
Gnomad MID
AF:
0.763
Gnomad NFE
AF:
0.670
Gnomad OTH
AF:
0.718
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.729
AC:
110783
AN:
152036
Hom.:
41716
Cov.:
31
AF XY:
0.724
AC XY:
53738
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.922
Gnomad4 AMR
AF:
0.592
Gnomad4 ASJ
AF:
0.685
Gnomad4 EAS
AF:
0.576
Gnomad4 SAS
AF:
0.745
Gnomad4 FIN
AF:
0.629
Gnomad4 NFE
AF:
0.670
Gnomad4 OTH
AF:
0.721
Alfa
AF:
0.684
Hom.:
6222
Bravo
AF:
0.731
Asia WGS
AF:
0.655
AC:
2282
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.26
DANN
Benign
0.59

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: rs230520; hg19: chr4-103465612; API