14-35401929-TTTC-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020529.3(NFKBIA):c.*81_*83del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,522,486 control chromosomes in the GnomAD database, including 8,207 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (930 hom., cov: 32)
  • Exomes 𝑓: 0.086 (7277 hom.)
• Consequence: NFKBIA NM_020529.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.440

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 14-35401929-TTTC-T is Benign according to our data. Variant chr14-35401929-TTTC-T is described in ClinVar as [Benign]. Clinvar id is 313106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIA	NM_020529.3	c.*81_*83del		3_prime_UTR_variant	6/6	ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10	c.*81_*83del		3_prime_UTR_variant	6/6	1	NM_020529.3	P1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12881 AN: 152082 Hom.: 925 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0907

GnomAD4 exome AF: 0.0856 AC: 117300 AN: 1370286 Hom.: 7277 AF XY: 0.0865 AC XY: 59375 AN XY: 686264

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0604

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0775

Gnomad4 NFE exome AF: 0.0679

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0848 AC: 12900 AN: 152200 Hom.: 930 Cov.: 32 AF XY: 0.0902 AC XY: 6711 AN XY: 74404

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0898

Bravo AF: 0.0956

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Ectodermal dysplasia and immunodeficiency 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs145753299; hg19: chr14-35871135;