rs677011

Variant names:

• chr3-101855659-G-A
• rs677011
• NM_031419.4:c.1655-74G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000326172.9(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 ENST00000326172.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326172.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	NM_031419.4	MANE Select	c.1655-74G>A		intron	N/A	NP_113607.1
	NFKBIZ	NM_001005474.3		c.1355-74G>A		intron	N/A	NP_001005474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	ENST00000326172.9	TSL:1 MANE Select	c.1655-74G>A		intron	N/A	ENSP00000325663.5
	NFKBIZ	ENST00000394054.6	TSL:1	c.1355-74G>A		intron	N/A	ENSP00000377618.2
	NFKBIZ	ENST00000465476.1	TSL:3	n.448G>A		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.505 AC: 14705 AN: 29098

American (AMR) AF: 0.747 AC: 22878 AN: 30616

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 12657 AN: 20174

East Asian (EAS) AF: 0.454 AC: 17587 AN: 38750

South Asian (SAS) AF: 0.517 AC: 36004 AN: 69614

European-Finnish (FIN) AF: 0.549 AC: 27375 AN: 49854

Middle Eastern (MID) AF: 0.590 AC: 3004 AN: 5090

European-Non Finnish (NFE) AF: 0.680 AC: 688926 AN: 1013838

Other (OTH) AF: 0.634 AC: 34551 AN: 54490

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

African (AFR) AF: 0.520 AC: 21569 AN: 41448

American (AMR) AF: 0.694 AC: 10606 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2166 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2357 AN: 5170

South Asian (SAS) AF: 0.500 AC: 2409 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5748 AN: 10542

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.657 AC: 44667 AN: 67980

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.642 Hom.: 92658

Bravo AF: 0.617

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.27
PhyloP100		0.17
PromoterAI		-0.016	Neutral
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: rs677011; hg19: chr3-101574503; COSMIC: COSV58199911; COSMIC: COSV58199911;