Variant 14-35403101-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.547+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,587,476 control chromosomes in the GnomAD database, including 23,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1581 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21920 hom. )

Consequence

NFKBIA
NM_020529.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.67

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=-0.79).

BP6

Variant 14-35403101-C-T is Benign according to our data. Variant chr14-35403101-C-T is described in ClinVar as [Benign]. Clinvar id is 1290379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIA	NM_020529.3 linkuse as main transcript	c.547+49G>A		intron_variant		ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10 linkuse as main transcript	c.547+49G>A		intron_variant		1	NM_020529.3	P1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20187

AN:

152114

Hom.:

1577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0982

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0146

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.136

AC:

32469

AN:

239468

Hom.:

2556

AF XY:

0.140

AC XY:

18121

AN XY:

129502

show subpopulations

Gnomad AFR exome

AF:

0.0744

Gnomad AMR exome

AF:

0.0736

Gnomad ASJ exome

AF:

0.0985

Gnomad EAS exome

AF:

0.0124

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.170

AC:

243575

AN:

1435244

Hom.:

21920

Cov.:

AF XY:

0.169

AC XY:

120262

AN XY:

712358

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.0762

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.133

AC:

20196

AN:

152232

Hom.:

1581

Cov.:

AF XY:

0.129

AC XY:

9631

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0749

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.121

Hom.:

399

Bravo

AF:

0.125

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.020

Dann

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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