rs8904

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020529.3(NFKBIA):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,611,958 control chromosomes in the GnomAD database, including 121,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15318 hom., cov: 31)

Exomes 𝑓: 0.38 ( 106090 hom. )

Consequence

NFKBIA
NM_020529.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.295

Variant links:

Genes affected

NFKBIA (HGNC:7797): (NFKB inhibitor alpha) This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]

NFKBIA links:

NFKBIA (HGNC:):

NFKBIA 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=-0.78).

BP6

Variant 14-35402011-G-A is Benign according to our data. Variant chr14-35402011-G-A is described in ClinVar as [Benign]. Clinvar id is 313108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-35402011-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIA	NM_020529.3 linkuse as main transcript	c.*2C>T		3_prime_UTR_variant	6/6	ENST00000216797.10	NP_065390.1	P25963

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIA	ENST00000216797 linkuse as main transcript	c.*2C>T		3_prime_UTR_variant	6/6	1	NM_020529.3	ENSP00000216797.6		P25963

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66218

AN:

151384

Hom.:

15298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.425

GnomAD3 exomes

AF:

0.393

AC:

98581

AN:

251136

Hom.:

19908

AF XY:

0.395

AC XY:

53624

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.421

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.377

AC:

550843

AN:

1460456

Hom.:

106090

Cov.:

AF XY:

0.378

AC XY:

274984

AN XY:

726578

show subpopulations

Gnomad4 AFR exome

AF:

0.608

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.359

Gnomad4 SAS exome

AF:

0.411

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.437

AC:

66282

AN:

151502

Hom.:

15318

Cov.:

AF XY:

0.435

AC XY:

32217

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.595

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.398

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.433

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.390

Hom.:

23172

Bravo

AF:

0.435

Asia WGS

AF:

0.418

AC:

1453

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Ectodermal dysplasia and immunodeficiency 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

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

-0.78

CADD

Benign

0.27

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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