Variant 14-35402888-C-T 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.548-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,597,270 control chromosomes in the GnomAD database, including 25,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1639 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23939 hom. )

Consequence

NFKBIA
NM_020529.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.415

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=-0.77).

BP6

Variant 14-35402888-C-T is Benign according to our data. Variant chr14-35402888-C-T is described in ClinVar as [Benign]. Clinvar id is 1260146.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.548-29G>A		intron_variant		ENST00000216797.10	NP_065390.1	P25963

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIA	ENST00000216797.10 linkuse as main transcript	c.548-29G>A		intron_variant		1	NM_020529.3	ENSP00000216797.6		P25963

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20306

AN:

152096

Hom.:

1640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0138

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.141

AC:

34599

AN:

245658

Hom.:

2808

AF XY:

0.146

AC XY:

19452

AN XY:

133148

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.0788

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.177

AC:

255406

AN:

1445056

Hom.:

23939

Cov.:

AF XY:

0.176

AC XY:

126751

AN XY:

719858

show subpopulations

Gnomad4 AFR exome

AF:

0.0610

Gnomad4 AMR exome

AF:

0.0819

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.0175

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.133

AC:

20309

AN:

152214

Hom.:

1639

Cov.:

AF XY:

0.130

AC XY:

9677

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0611

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0139

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.138

Hom.:

358

Bravo

AF:

0.126

Asia WGS

AF:

0.0770

AC:

272

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

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.77

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