dbSNP rs28362491: NFKB1:c.-794_-791delATTG (chr4-102500997-CATTG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000966659.1(NFKB1):c.-794_-791delATTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 153,546 control chromosomes in the GnomAD database, including 14,272 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14166 hom., cov: 0)

Exomes 𝑓: 0.32 ( 106 hom. )

Consequence

NFKB1
ENST00000966659.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Publications

329 publications found

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]

NFKB1 Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 12
Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NFKB1 links:

ENSG00000260651 (HGNC:):

ENSG00000260651 links:

NFKB1-AS1 (HGNC:58149):

NFKB1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000966659.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000966659.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKB1-AS1	NR_136202.1		n.48+1438_48+1441delCAAT		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NFKB1	ENST00000966659.1		c.-794_-791delATTG	5_prime_UTR	Exon 1 of 24	ENSP00000636718.1
ENSG00000260651	ENST00000563833.1	TSL:6	n.319_322delCAAT	non_coding_transcript_exon	Exon 1 of 1
NFKB1-AS1	ENST00000843825.1		n.49+1438_49+1441delCAAT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64938

AN:

151662

Hom.:

14138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.323

AC:

570

AN:

1764

Hom.:

106

AF XY:

0.327

AC XY:

353

AN XY:

1080

show subpopulations

African (AFR)

AF:

0.350

AC:

AN:

American (AMR)

AF:

0.429

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

AN:

East Asian (EAS)

AF:

0.313

AC:

AN:

160

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.489

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.331

AC:

421

AN:

1270

Other (OTH)

AF:

0.256

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.428

AC:

65010

AN:

151782

Hom.:

14166

Cov.:

AF XY:

0.429

AC XY:

31815

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.494

AC:

20462

AN:

41388

American (AMR)

AF:

0.485

AC:

7412

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1155

AN:

3468

East Asian (EAS)

AF:

0.403

AC:

2073

AN:

5150

South Asian (SAS)

AF:

0.297

AC:

1435

AN:

4826

European-Finnish (FIN)

AF:

0.447

AC:

4714

AN:

10542

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.391

AC:

26510

AN:

67844

Other (OTH)

AF:

0.398

AC:

836

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1910

3820

5731

7641

9551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.416

Hom.:

1645

Bravo

AF:

0.439

Asia WGS

AF:

0.354

AC:

1226

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.072

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over