Variant rs4648049 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.1210+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,603,918 control chromosomes in the GnomAD database, including 2,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 406 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1640 hom. )

Consequence

NFKB1
NM_003998.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.05

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:

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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=-0.93).

BP6

Variant 4-102593580-C-T is Benign according to our data. Variant chr4-102593580-C-T is described in ClinVar as [Benign]. Clinvar id is 1168687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKB1	NM_003998.4 link	c.1210+12C>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 link	c.1210+12C>T		intron_variant		1	NM_003998.4	ENSP00000226574.4		P19838-2
NFKB1	ENST00000505458.5 link	c.1207+12C>T		intron_variant		1		ENSP00000424790.1		P19838-1

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9902

AN:

152052

Hom.:

401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0504

Gnomad SAS

AF:

0.0340

Gnomad FIN

AF:

0.0654

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0518

GnomAD3 exomes

AF:

0.0462

AC:

11217

AN:

243016

Hom.:

357

AF XY:

0.0447

AC XY:

5877

AN XY:

131496

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0630

Gnomad SAS exome

AF:

0.0282

Gnomad FIN exome

AF:

0.0619

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0413

GnomAD4 exome

AF:

0.0448

AC:

65026

AN:

1451748

Hom.:

1640

Cov.:

AF XY:

0.0443

AC XY:

31985

AN XY:

722378

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0517

Gnomad4 SAS exome

AF:

0.0280

Gnomad4 FIN exome

AF:

0.0618

Gnomad4 NFE exome

AF:

0.0444

Gnomad4 OTH exome

AF:

0.0460

GnomAD4 genome

AF:

0.0653

AC:

9940

AN:

152170

Hom.:

406

Cov.:

AF XY:

0.0657

AC XY:

4887

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.0500

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0654

Gnomad4 NFE

AF:

0.0453

Gnomad4 OTH

AF:

0.0513

Alfa

AF:

0.0479

Hom.:

Bravo

AF:

0.0667

Asia WGS

AF:

0.0540

AC:

186

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
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

-0.93

CADD

Benign

0.054

DANN

Benign

0.40

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