rs677011

Positions:

• chr3-101855659-G-A
• chr3-101855659-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031419.4(NFKBIZ):​c.1655-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,463,558 control chromosomes in the GnomAD database, including 311,963 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 0.60 (28066 hom., cov: 32)
  • Exomes 𝑓: 0.65 (283897 hom.)
• Consequence: NFKBIZ NM_031419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIZ	NM_031419.4	c.1655-74G>A		intron_variant		ENST00000326172.9
NFKBIZ	NM_001005474.3	c.1355-74G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIZ	ENST00000326172.9	c.1655-74G>A		intron_variant		1	NM_031419.4	P4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91479 AN: 151916 Hom.: 28042 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.654 AC: 857687 AN: 1311524 Hom.: 283897 Cov.: 20 AF XY: 0.650 AC XY: 421236 AN XY: 648546

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.602 AC: 91565 AN: 152034 Hom.: 28066 Cov.: 32 AF XY: 0.595 AC XY: 44226 AN XY: 74326

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.615

Alfa AF: 0.651 Hom.: 53729

Bravo AF: 0.617

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.27

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: rs677011; hg19: chr3-101574503; COSMIC: COSV58199911; COSMIC: COSV58199911;