Variant rs2233419 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_020529.3(NFKBIA):c.636+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,940 control chromosomes in the GnomAD database, including 26,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1899 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24732 hom. )

Consequence

NFKBIA
NM_020529.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.163

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:

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=-0.87).

BP6

Variant 14-35402754-G-A is Benign according to our data. Variant chr14-35402754-G-A is described in ClinVar as [Benign]. Clinvar id is 1166715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 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.636+17C>T		intron_variant		ENST00000216797.10	NP_065390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIA	ENST00000216797.10 linkuse as main transcript	c.636+17C>T		intron_variant		1	NM_020529.3	ENSP00000216797	P1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22922

AN:

152060

Hom.:

1899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.153

AC:

38554

AN:

251316

Hom.:

3223

AF XY:

0.156

AC XY:

21143

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0995

Gnomad EAS exome

AF:

0.0257

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.180

AC:

263744

AN:

1461762

Hom.:

24732

Cov.:

AF XY:

0.179

AC XY:

130388

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0369

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.151

AC:

22940

AN:

152178

Hom.:

1899

Cov.:

AF XY:

0.148

AC XY:

10978

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.0331

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.158

Hom.:

626

Bravo

AF:

0.147

Asia WGS

AF:

0.0990

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Ectodermal dysplasia and immunodeficiency 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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