chr3-101850882-A-C

Variant names:

• chr3-101850882-A-C
• rs616597
• NM_031419.4:c.289+965A>C

Variant summary

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

The NM_031419.4(NFKBIZ):​c.289+965A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,218 control chromosomes in the GnomAD database, including 50,687 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 (50687 hom., cov: 33)
• Consequence: NFKBIZ NM_031419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 19 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: AD 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIZ	NM_031419.4	c.289+965A>C		intron_variant	Intron 1 of 11	ENST00000326172.9	NP_113607.1
NFKBIZ	NM_001005474.3	c.-11-1203A>C		intron_variant	Intron 2 of 12		NP_001005474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIZ	ENST00000326172.9	c.289+965A>C		intron_variant	Intron 1 of 11	1	NM_031419.4	ENSP00000325663.5

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123362 AN: 152100 Hom.: 50629 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.708

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.811 AC: 123482 AN: 152218 Hom.: 50687 Cov.: 33 AF XY: 0.806 AC XY: 59975 AN XY: 74418

African (AFR) AF: 0.929 AC: 38626 AN: 41562

American (AMR) AF: 0.812 AC: 12424 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2793 AN: 3472

East Asian (EAS) AF: 0.615 AC: 3176 AN: 5168

South Asian (SAS) AF: 0.820 AC: 3947 AN: 4812

European-Finnish (FIN) AF: 0.690 AC: 7299 AN: 10584

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.772 AC: 52491 AN: 68010

Other (OTH) AF: 0.812 AC: 1714 AN: 2112

Alfa AF: 0.784 Hom.: 151917

Bravo AF: 0.827

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs616597; hg19: chr3-101569726;