Variant rs4648110 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.2592+58T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,468,294 control chromosomes in the GnomAD database, including 31,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3979 hom., cov: 32)

Exomes 𝑓: 0.20 ( 27328 hom. )

Consequence

NFKB1
NM_003998.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.582

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=-0.9).

BP6

Variant 4-102612664-T-A is Benign according to our data. Variant chr4-102612664-T-A is described in ClinVar as [Benign]. Clinvar id is 1256826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.2592+58T>A		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.2592+58T>A		intron_variant		1	NM_003998.4	ENSP00000226574	P4	P19838-2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32923

AN:

151980

Hom.:

3980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.0603

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.235

GnomAD4 exome

AF:

0.197

AC:

259852

AN:

1316196

Hom.:

27328

AF XY:

0.199

AC XY:

130971

AN XY:

658598

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.0689

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.216

AC:

32923

AN:

152098

Hom.:

3979

Cov.:

AF XY:

0.211

AC XY:

15711

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.0604

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.210

Hom.:

427

Bravo

AF:

0.220

Asia WGS

AF:

0.132

AC:

458

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

DANN

Benign

0.65

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