3-101857560-A-T

Variant names:

• chr3-101857560-A-T
• rs622122
• NM_031419.4:c.2103+101A>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.2103+101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,541,860 control chromosomes in the GnomAD database, including 290,323 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 0.54 (23414 hom., cov: 33)
  • Exomes 𝑓: 0.62 (266909 hom.)
• Consequence: NFKBIZ NM_031419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 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.2103+101A>T		intron	N/A	NP_113607.1	Q9BYH8-1
	NFKBIZ	NM_001005474.3		c.1803+101A>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.2103+101A>T		intron	N/A	ENSP00000325663.5	Q9BYH8-1
	NFKBIZ	ENST00000394054.6	TSL:1	c.1803+101A>T		intron	N/A	ENSP00000377618.2	Q9BYH8-2
	NFKBIZ	ENST00000326151.9	TSL:2	c.1737+101A>T		intron	N/A	ENSP00000325593.5	Q9BYH8-3

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82728 AN: 151924 Hom.: 23397 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.616 AC: 856441 AN: 1389818 Hom.: 266909 Cov.: 40 AF XY: 0.612 AC XY: 419271 AN XY: 684592

African (AFR) AF: 0.374 AC: 12118 AN: 32394

American (AMR) AF: 0.727 AC: 27425 AN: 37730

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 13835 AN: 22390

East Asian (EAS) AF: 0.453 AC: 17556 AN: 38752

South Asian (SAS) AF: 0.504 AC: 38119 AN: 75646

European-Finnish (FIN) AF: 0.532 AC: 22181 AN: 41680

Middle Eastern (MID) AF: 0.565 AC: 2192 AN: 3882

European-Non Finnish (NFE) AF: 0.638 AC: 688547 AN: 1079590

Other (OTH) AF: 0.597 AC: 34468 AN: 57754

GnomAD4 genome AF: 0.545 AC: 82792 AN: 152042 Hom.: 23414 Cov.: 33 AF XY: 0.540 AC XY: 40123 AN XY: 74306

African (AFR) AF: 0.390 AC: 16158 AN: 41482

American (AMR) AF: 0.661 AC: 10112 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2147 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2356 AN: 5164

South Asian (SAS) AF: 0.490 AC: 2366 AN: 4830

European-Finnish (FIN) AF: 0.530 AC: 5577 AN: 10518

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42177 AN: 67972

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.563 Hom.: 3076

Bravo AF: 0.554

Asia WGS AF: 0.454 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs622122; hg19: chr3-101576404; COSMIC: COSV58202555; COSMIC: COSV58202555;