3-101855276-G-A

Variant names:

• chr3-101855276-G-A
• rs7644329
• NM_031419.4:c.1590+68G>A

Variant summary

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

The NM_031419.4(NFKBIZ):​c.1590+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00631 in 1,599,186 control chromosomes in the GnomAD database, including 552 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 0.034 (303 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (249 hom.)
• Consequence: NFKBIZ NM_031419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIZ	NM_031419.4	MANE Select	c.1590+68G>A		intron	N/A	NP_113607.1
	NFKBIZ	NM_001005474.3		c.1290+68G>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.1590+68G>A		intron	N/A	ENSP00000325663.5
	NFKBIZ	ENST00000394054.6	TSL:1	c.1290+68G>A		intron	N/A	ENSP00000377618.2
	NFKBIZ	ENST00000483180.5	TSL:5	c.1290+68G>A		intron	N/A	ENSP00000419800.1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5205 AN: 152144 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.00337 AC: 4869 AN: 1446924 Hom.: 249 Cov.: 30 AF XY: 0.00286 AC XY: 2055 AN XY: 718594

African (AFR) AF: 0.121 AC: 3974 AN: 32910

American (AMR) AF: 0.00675 AC: 291 AN: 43116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.000366 AC: 31 AN: 84610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52888

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5700

European-Non Finnish (NFE) AF: 0.000138 AC: 152 AN: 1103246

Other (OTH) AF: 0.00685 AC: 409 AN: 59734

GnomAD4 genome AF: 0.0343 AC: 5223 AN: 152262 Hom.: 303 Cov.: 32 AF XY: 0.0338 AC XY: 2516 AN XY: 74450

African (AFR) AF: 0.119 AC: 4939 AN: 41542

American (AMR) AF: 0.0141 AC: 216 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0126 Hom.: 116

Bravo AF: 0.0389

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.37
PhyloP100		-0.36
PromoterAI		-0.0066	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: rs7644329; hg19: chr3-101574120;