3-101851531-A-T

Variant names:

• chr3-101851531-A-T
• rs600718
• NM_031419.4:c.290-554A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

NFKBIZ Gene-Disease associations (from GenCC):

• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

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 = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031419.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	NM_031419.4	MANE Select	c.290-554A>T		intron	N/A	NP_113607.1	Q9BYH8-1
	NFKBIZ	NM_001005474.3		c.-11-554A>T		intron	N/A	NP_001005474.1	Q9BYH8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	ENST00000326172.9	TSL:1 MANE Select	c.290-554A>T		intron	N/A	ENSP00000325663.5	Q9BYH8-1
	NFKBIZ	ENST00000394054.6	TSL:1	c.-11-554A>T		intron	N/A	ENSP00000377618.2	Q9BYH8-2
	NFKBIZ	ENST00000483180.5	TSL:5	c.-11-554A>T		intron	N/A	ENSP00000419800.1	C9JZ23

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

African (AFR) AF: 0.929 AC: 38604 AN: 41562

American (AMR) AF: 0.805 AC: 12314 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2766 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3172 AN: 5178

South Asian (SAS) AF: 0.821 AC: 3965 AN: 4828

European-Finnish (FIN) AF: 0.688 AC: 7280 AN: 10586

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52084 AN: 68002

Other (OTH) AF: 0.805 AC: 1701 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.4
DANN	Benign	0.68
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs600718; hg19: chr3-101570375;