Variant 4-102593288-C-G 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.1067-137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 808,716 control chromosomes in the GnomAD database, including 68,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13248 hom., cov: 32)

Exomes 𝑓: 0.40 ( 55048 hom. )

Consequence

NFKB1
NM_003998.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.05

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:

NFKB1 (HGNC:):

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=-0.73).

BP6

Variant 4-102593288-C-G is Benign according to our data. Variant chr4-102593288-C-G is described in ClinVar as [Benign]. Clinvar id is 1272513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 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.1067-137C>G		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.1067-137C>G		intron_variant		1	NM_003998.4	ENSP00000226574.4		P19838-2
NFKB1	ENST00000505458.5 linkuse as main transcript	c.1064-137C>G		intron_variant		1		ENSP00000424790.1		P19838-1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62984

AN:

151854

Hom.:

13212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.398

GnomAD4 exome

AF:

0.403

AC:

264768

AN:

656744

Hom.:

55048

Cov.:

AF XY:

0.398

AC XY:

136045

AN XY:

341888

show subpopulations

Gnomad4 AFR exome

AF:

0.394

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.425

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.442

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.415

AC:

63064

AN:

151972

Hom.:

13248

Cov.:

AF XY:

0.418

AC XY:

31050

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.417

Hom.:

1646

Bravo

AF:

0.420

Asia WGS

AF:

0.425

AC:

1474

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

-0.73

CADD

Benign

DANN

Benign

0.76

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