3-101851531-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031419.4(NFKBIZ):c.290-554A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,242 control chromosomes in the GnomAD database, including 50,212 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 0.81 (50212 hom., cov: 33)
• Consequence: NFKBIZ NM_031419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

Genes affected

NFKBIZ (HGNC:29805): (NFKB inhibitor zeta) This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. Studies in mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6 production. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIZ	NM_031419.4	c.290-554A>T		intron_variant		ENST00000326172.9
NFKBIZ	NM_001005474.3	c.-11-554A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIZ	ENST00000326172.9	c.290-554A>T		intron_variant		1	NM_031419.4	P4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122778 AN: 152124 Hom.: 50153 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.807 AC: 122899 AN: 152242 Hom.: 50212 Cov.: 33 AF XY: 0.802 AC XY: 59698 AN XY: 74432

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.805

Alfa AF: 0.670 Hom.: 1796

Bravo AF: 0.823

Asia WGS AF: 0.736 AC: 2562 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	9.4
Dann	Benign	0.68

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: rs600718; hg19: chr3-101570375;