rs1957106

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020529.3(NFKBIA):c.81C>T(p.Asp27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,591,188 control chromosomes in the GnomAD database, including 68,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5326 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62932 hom. )

Consequence

NFKBIA
NM_020529.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 0.0270

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 14-35404564-G-A is Benign according to our data. Variant chr14-35404564-G-A is described in ClinVar as [Benign]. Clinvar id is 313117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-35404564-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.027 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 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.81C>T	p.Asp27=	synonymous_variant	1/6	ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10 linkuse as main transcript	c.81C>T	p.Asp27=	synonymous_variant	1/6	1	NM_020529.3	P1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38116

AN:

151672

Hom.:

5315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.284

AC:

61676

AN:

217444

Hom.:

9164

AF XY:

0.292

AC XY:

35000

AN XY:

120014

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.265

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.292

AC:

419627

AN:

1439408

Hom.:

62932

Cov.:

AF XY:

0.293

AC XY:

209963

AN XY:

715466

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.297

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.251

AC:

38147

AN:

151780

Hom.:

5326

Cov.:

AF XY:

0.255

AC XY:

18942

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.280

Hom.:

7833

Bravo

AF:

0.229

Asia WGS

AF:

0.295

AC:

1001

AN:

3406

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ectodermal dysplasia and immunodeficiency 2

Benign:3

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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:2

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 -
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 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

Cadd

Benign

9.4

Dann

Benign

0.95

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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