14-35402201-A-G

Position:

• chr14-35402201-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020529.3(NFKBIA):​c.907-141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 1,192,596 control chromosomes in the GnomAD database, including 375,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (49107 hom., cov: 29)
  • Exomes 𝑓: 0.79 (326135 hom.)
• Consequence: NFKBIA NM_020529.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-35402201-A-G is Benign according to our data. Variant chr14-35402201-A-G is described in ClinVar as [Benign]. Clinvar id is 1279397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIA	NM_020529.3	c.907-141T>C		intron_variant		ENST00000216797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIA	ENST00000216797.10	c.907-141T>C		intron_variant		1	NM_020529.3	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 121803 AN: 151396 Hom.: 49052 Cov.: 29

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.790 AC: 822398 AN: 1041082 Hom.: 326135 AF XY: 0.792 AC XY: 423481 AN XY: 534474

Gnomad4 AFR exome AF: 0.810

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.682

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.784

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.805 AC: 121919 AN: 151514 Hom.: 49107 Cov.: 29 AF XY: 0.804 AC XY: 59463 AN XY: 73940

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.787

Alfa AF: 0.798 Hom.: 46479

Bravo AF: 0.806

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs1022714; hg19: chr14-35871407;