Variant chr14-35403586-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_020529.3(NFKBIA):c.336+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 885,522 control chromosomes in the GnomAD database, including 240,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35846 hom., cov: 31)

Exomes 𝑓: 0.74 ( 205036 hom. )

Consequence

NFKBIA
NM_020529.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.962

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-35403586-A-G is Benign according to our data. Variant chr14-35403586-A-G is described in ClinVar as [Benign]. Clinvar id is 1283234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 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.336+104T>C		intron_variant		ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10 linkuse as main transcript	c.336+104T>C		intron_variant		1	NM_020529.3	P1

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102260

AN:

151912

Hom.:

35815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.646

GnomAD4 exome

AF:

0.744

AC:

545488

AN:

733492

Hom.:

205036

Cov.:

AF XY:

0.748

AC XY:

289117

AN XY:

386288

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.789

Gnomad4 ASJ exome

AF:

0.656

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.839

Gnomad4 FIN exome

AF:

0.818

Gnomad4 NFE exome

AF:

0.746

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.673

AC:

102343

AN:

152030

Hom.:

35846

Cov.:

AF XY:

0.679

AC XY:

50469

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.729

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.640

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.752

Gnomad4 OTH

AF:

0.649

Alfa

AF:

0.681

Hom.:

5648

Bravo

AF:

0.654

Asia WGS

AF:

0.757

AC:

2633

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	Nov 12, 2018	- -

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 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.057

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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