chr14-35401248-C-T

Variant names:

• chr14-35401248-C-T
• rs3138055
• ENST00000697954.1:n.1928G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000697954.1(NFKBIA):​n.1928G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,130 control chromosomes in the GnomAD database, including 38,529 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38529 hom., cov: 33)
• Consequence: NFKBIA ENST00000697954.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIA	ENST00000697954.1	n.1928G>A		non_coding_transcript_exon_variant	Exon 2 of 2
NFKBIA	ENST00000697955.1	n.1967G>A		non_coding_transcript_exon_variant	Exon 3 of 3
NFKBIA	ENST00000697956.1	n.1995G>A		non_coding_transcript_exon_variant	Exon 3 of 3
NFKBIA	ENST00000697957.1	n.2114G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107622 AN: 152012 Hom.: 38496 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.708 AC: 107715 AN: 152130 Hom.: 38529 Cov.: 33 AF XY: 0.702 AC XY: 52234 AN XY: 74370

African (AFR) AF: 0.740 AC: 30705 AN: 41494

American (AMR) AF: 0.610 AC: 9332 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2294 AN: 5182

South Asian (SAS) AF: 0.721 AC: 3468 AN: 4812

European-Finnish (FIN) AF: 0.726 AC: 7681 AN: 10586

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49785 AN: 67982

Other (OTH) AF: 0.682 AC: 1438 AN: 2110

Alfa AF: 0.720 Hom.: 54980

Bravo AF: 0.698

Asia WGS AF: 0.589 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.032
DANN	Benign	0.64
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs3138055; hg19: chr14-35870454;