Variant rs4648117 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 ENST00000226574.9(NFKB1):c.2593-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,609,468 control chromosomes in the GnomAD database, including 1,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 128 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1357 hom. )

Consequence

NFKB1
ENST00000226574.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0730

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:

LOC105377347 (HGNC:):

LOC105377347 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-102613400-C-T is Benign according to our data. Variant chr4-102613400-C-T is described in ClinVar as [Benign]. Clinvar id is 1287389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0563 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.2593-25C>T		intron_variant		ENST00000226574.9	NP_003989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKB1	ENST00000226574.9 linkuse as main transcript	c.2593-25C>T		intron_variant		1	NM_003998.4	ENSP00000226574	P4	P19838-2

Frequencies

GnomAD3 genomes

AF:

0.0387

AC:

5889

AN:

152114

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0623

Gnomad SAS

AF:

0.0341

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0405

AC:

10091

AN:

249444

Hom.:

250

AF XY:

0.0407

AC XY:

5486

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0769

Gnomad SAS exome

AF:

0.0300

Gnomad FIN exome

AF:

0.0616

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0423

AC:

61694

AN:

1457236

Hom.:

1357

Cov.:

AF XY:

0.0421

AC XY:

30520

AN XY:

724288

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0585

Gnomad4 SAS exome

AF:

0.0286

Gnomad4 FIN exome

AF:

0.0619

Gnomad4 NFE exome

AF:

0.0445

Gnomad4 OTH exome

AF:

0.0402

GnomAD4 genome

AF:

0.0387

AC:

5896

AN:

152232

Hom.:

128

Cov.:

AF XY:

0.0393

AC XY:

2924

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.0282

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.0619

Gnomad4 SAS

AF:

0.0347

Gnomad4 FIN

AF:

0.0657

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0367

Hom.:

Bravo

AF:

0.0359

Asia WGS

AF:

0.0480

AC:

165

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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.2

DANN

Benign

0.44

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