14-35401869-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020529.3(NFKBIA):c.*143_*144insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 879,284 control chromosomes in the GnomAD database, including 378 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (63 hom., cov: 32)
  • Exomes 𝑓: 0.025 (315 hom.)
• Consequence: NFKBIA NM_020529.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.218

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 -10 ACMG points.

• BP6: Variant 14-35401869-C-CAA is Benign according to our data. Variant chr14-35401869-C-CAA is described in ClinVar as [Likely_benign]. Clinvar id is 313104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIA	NM_020529.3	c.*143_*144insTT		3_prime_UTR_variant	6/6	ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10	c.*143_*144insTT		3_prime_UTR_variant	6/6	1	NM_020529.3	P1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3491 AN: 152200 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.0249 AC: 18066 AN: 726966 Hom.: 315 Cov.: 9 AF XY: 0.0256 AC XY: 9832 AN XY: 384288

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.00906

Gnomad4 EAS exome AF: 0.0544

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0230 AC: 3498 AN: 152318 Hom.: 63 Cov.: 32 AF XY: 0.0229 AC XY: 1703 AN XY: 74476

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0200 Hom.: 5

Bravo AF: 0.0229

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ectodermal dysplasia and immunodeficiency 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11569610; hg19: chr14-35871075;