Variant rs4648095 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.1954+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,601,214 control chromosomes in the GnomAD database, including 1,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 282 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1528 hom. )

Consequence

NFKB1
NM_003998.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.505

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=-0.9).

BP6

Variant 4-102606719-T-C is Benign according to our data. Variant chr4-102606719-T-C is described in ClinVar as [Benign]. Clinvar id is 1289420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 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.1954+22T>C		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.1954+22T>C		intron_variant		1	NM_003998.4	ENSP00000226574.4		P19838-2
NFKB1	ENST00000505458.5 linkuse as main transcript	c.1951+22T>C		intron_variant		1		ENSP00000424790.1		P19838-1

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8688

AN:

152160

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0887

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0630

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.0655

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0460

AC:

10932

AN:

237908

Hom.:

300

AF XY:

0.0451

AC XY:

5795

AN XY:

128476

show subpopulations

Gnomad AFR exome

AF:

0.0902

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.0778

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.0625

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0445

AC:

64487

AN:

1448936

Hom.:

1528

Cov.:

AF XY:

0.0441

AC XY:

31763

AN XY:

719584

show subpopulations

Gnomad4 AFR exome

AF:

0.0939

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.0586

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.0620

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0450

GnomAD4 genome

AF:

0.0571

AC:

8701

AN:

152278

Hom.:

282

Cov.:

AF XY:

0.0570

AC XY:

4245

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0887

Gnomad4 AMR

AF:

0.0350

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.0625

Gnomad4 SAS

AF:

0.0353

Gnomad4 FIN

AF:

0.0655

Gnomad4 NFE

AF:

0.0453

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0444

Hom.:

Bravo

AF:

0.0571

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.90

CADD

Benign

0.073

DANN

Benign

0.57

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.

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