rs622122

Positions:

• chr3-101857560-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.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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIZ	NM_031419.4	c.2103+101A>T		intron_variant		ENST00000326172.9	NP_113607.1
NFKBIZ	NM_001005474.3	c.1803+101A>T		intron_variant			NP_001005474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIZ	ENST00000326172.9	c.2103+101A>T		intron_variant		1	NM_031419.4	ENSP00000325663	P4

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

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.727

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.597

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

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.567

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs622122; hg19: chr3-101576404; COSMIC: COSV58202555; COSMIC: COSV58202555;