rs1957106

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020529.3(NFKBIA):c.81C>T(p.Asp27Asp) 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:6O:1

Conservation

PhyloP100: 0.0270

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

ectodermal dysplasia and immunodeficiency 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ectodermal dysplasia and immune deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NFKBIA links:

ENSG00000310246 (HGNC:):

ENSG00000310246 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 313117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
NFKBIA	NM_020529.3 link	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 6	ENST00000216797.10	NP_065390.1	P25963

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIA	ENST00000216797.10 link	c.81C>T	p.Asp27Asp	synonymous_variant	Exon 1 of 6	1	NM_020529.3	ENSP00000216797.6		P25963

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

GnomAD2 exomes

AF:

0.284

AC:

61676

AN:

217444

AF XY:

0.292

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 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

African (AFR)

AF:

0.136

AC:

4357

AN:

31998

American (AMR)

AF:

0.182

AC:

7720

AN:

42330

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5438

AN:

25730

East Asian (EAS)

AF:

0.263

AC:

9913

AN:

37738

South Asian (SAS)

AF:

0.319

AC:

26607

AN:

83318

European-Finnish (FIN)

AF:

0.407

AC:

20639

AN:

50726

Middle Eastern (MID)

AF:

0.218

AC:

1248

AN:

5734

European-Non Finnish (NFE)

AF:

0.297

AC:

327276

AN:

1102406

Other (OTH)

AF:

0.276

AC:

16429

AN:

59428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15976

31952

47927

63903

79879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10632

21264

31896

42528

53160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38147

AN:

151780

Hom.:

5326

Cov.:

AF XY:

0.255

AC XY:

18942

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.145

AC:

5994

AN:

41470

American (AMR)

AF:

0.192

AC:

2926

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

715

AN:

3470

East Asian (EAS)

AF:

0.260

AC:

1336

AN:

5146

South Asian (SAS)

AF:

0.338

AC:

1629

AN:

4826

European-Finnish (FIN)

AF:

0.387

AC:

4054

AN:

10464

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.305

AC:

20716

AN:

67834

Other (OTH)

AF:

0.244

AC:

513

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1423

2846

4270

5693

7116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.274

Hom.:

10182

Bravo

AF:

0.229

Asia WGS

AF:

0.295

AC:

1001

AN:

3406

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ectodermal dysplasia and immunodeficiency 2

Benign:3

Nov 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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

(source)

DANN

Benign

0.95

PhyloP100

0.027

PromoterAI

0.0049

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over