rs645781

Variant names:

• chr3-101844136-G-A
• rs645781
• ENST00000394054.6:c.-11-7949G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-101844136-G-A
• chr3-101844136-G-C

Variant summary

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

The ENST00000394054.6(NFKBIZ):​c.-11-7949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,118 control chromosomes in the GnomAD database, including 47,765 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 0.79 (47765 hom., cov: 32)
• Consequence: NFKBIZ ENST00000394054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 7 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

ENSG00000297105 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIZ	NM_001005474.3	c.-11-7949G>A		intron_variant	Intron 2 of 12		NP_001005474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIZ	ENST00000394054.6	c.-11-7949G>A		intron_variant	Intron 2 of 12	1		ENSP00000377618.2
NFKBIZ	ENST00000483180.5	c.-11-7949G>A		intron_variant	Intron 1 of 10	5		ENSP00000419800.1
NFKBIZ	ENST00000461724.5	c.-737-4756G>A		intron_variant	Intron 2 of 3	5		ENSP00000418502.1
ENSG00000297105	ENST00000745520.1	n.167-869C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119860 AN: 151998 Hom.: 47707 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.789 AC: 119981 AN: 152118 Hom.: 47765 Cov.: 32 AF XY: 0.785 AC XY: 58377 AN XY: 74332

African (AFR) AF: 0.893 AC: 37069 AN: 41516

American (AMR) AF: 0.793 AC: 12128 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3323 AN: 5178

South Asian (SAS) AF: 0.823 AC: 3969 AN: 4822

European-Finnish (FIN) AF: 0.683 AC: 7191 AN: 10528

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51008 AN: 67998

Other (OTH) AF: 0.785 AC: 1661 AN: 2116

Alfa AF: 0.757 Hom.: 19617

Bravo AF: 0.803

Asia WGS AF: 0.749 AC: 2605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs645781; hg19: chr3-101562980;