Variant rs1609798 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003998.4(NFKB1):c.2750-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 772,700 control chromosomes in the GnomAD database, including 38,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6318 hom., cov: 32)

Exomes 𝑓: 0.31 ( 32024 hom. )

Consequence

NFKB1
NM_003998.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.16

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 links:

NFKB1 (HGNC:):

NFKB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-102616285-C-T is Benign according to our data. Variant chr4-102616285-C-T is described in ClinVar as [Benign]. Clinvar id is 1225916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKB1	NM_003998.4 linkuse as main transcript	c.2750-149C>T		intron_variant		ENST00000226574.9	NP_003989.2	P19838-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKB1	ENST00000226574.9 linkuse as main transcript	c.2750-149C>T		intron_variant		1	NM_003998.4	ENSP00000226574.4		P19838-2
NFKB1	ENST00000505458.5 linkuse as main transcript	c.2747-149C>T		intron_variant		1		ENSP00000424790.1		P19838-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40387

AN:

151984

Hom.:

6302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.312

AC:

193834

AN:

620596

Hom.:

32024

AF XY:

0.312

AC XY:

100810

AN XY:

323574

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.266

AC:

40408

AN:

152104

Hom.:

6318

Cov.:

AF XY:

0.270

AC XY:

20100

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.304

Hom.:

9785

Bravo

AF:

0.262

Asia WGS

AF:

0.356

AC:

1235

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.71

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over