rs3821727

Variant names:

• chr3-101853446-C-G
• rs3821727
• NM_031419.4:c.920C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-101853446-C-G
• chr3-101853446-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031419.4(NFKBIZ):​c.920C>G​(p.Thr307Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,614,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: NFKBIZ NM_031419.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004113525).

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.920C>G	p.Thr307Ser	missense	Exon 5 of 12	NP_113607.1	Q9BYH8-1
	NFKBIZ	NM_001005474.3		c.620C>G	p.Thr207Ser	missense	Exon 6 of 13	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.920C>G	p.Thr307Ser	missense	Exon 5 of 12	ENSP00000325663.5	Q9BYH8-1
	NFKBIZ	ENST00000394054.6	TSL:1	c.620C>G	p.Thr207Ser	missense	Exon 6 of 13	ENSP00000377618.2	Q9BYH8-2
	NFKBIZ	ENST00000483180.5	TSL:5	c.620C>G	p.Thr207Ser	missense	Exon 5 of 11	ENSP00000419800.1	C9JZ23

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00884

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000720 AC: 181 AN: 251476 AF XY: 0.000655

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000259 AC: 379 AN: 1461888 Hom.: 1 Cov.: 34 AF XY: 0.000254 AC XY: 185 AN XY: 727244

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00851 AC: 338 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.000232 AC: 14 AN: 60396

GnomAD4 genome AF: 0.000354 AC: 54 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74496

African (AFR) AF: 0.000120 AC: 5 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

East Asian (EAS) AF: 0.00886 AC: 46 AN: 5194

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000597

ExAC AF: 0.000667 AC: 81

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.89
DANN	Benign	0.16
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.12
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.046
Sift	Benign	0.93	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.060		Gain of glycosylation at T307 (P = 0.0834)
MVP		0.30
MPC		0.21
ClinPred		0.0056	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.10
Mutation Taster		=97/3	polymorphism

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: rs3821727; hg19: chr3-101572290;