Genetic Variant NFKBIZ:c.2103+101A>T (chr3-101857560-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.329

Publications

5 publications found

Variant links:

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

NFKBIZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFKBIZ	NM_031419.4 link	c.2103+101A>T		intron_variant	Intron 11 of 11	ENST00000326172.9	NP_113607.1	Q9BYH8-1
NFKBIZ	NM_001005474.3 link	c.1803+101A>T		intron_variant	Intron 12 of 12		NP_001005474.1	Q9BYH8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIZ	ENST00000326172.9 link	c.2103+101A>T		intron_variant	Intron 11 of 11	1	NM_031419.4	ENSP00000325663.5		Q9BYH8-1

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82728

AN:

151924

Hom.:

23397

Cov.:

show subpopulations

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.:

AF XY:

0.612

AC XY:

419271

AN XY:

684592

show subpopulations

African (AFR)

AF:

0.374

AC:

12118

AN:

32394

American (AMR)

AF:

0.727

AC:

27425

AN:

37730

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

13835

AN:

22390

East Asian (EAS)

AF:

0.453

AC:

17556

AN:

38752

South Asian (SAS)

AF:

0.504

AC:

38119

AN:

75646

European-Finnish (FIN)

AF:

0.532

AC:

22181

AN:

41680

Middle Eastern (MID)

AF:

0.565

AC:

2192

AN:

3882

European-Non Finnish (NFE)

AF:

0.638

AC:

688547

AN:

1079590

Other (OTH)

AF:

0.597

AC:

34468

AN:

57754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

17043

34085

51128

68170

85213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18608

37216

55824

74432

93040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.545

AC:

82792

AN:

152042

Hom.:

23414

Cov.:

AF XY:

0.540

AC XY:

40123

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.390

AC:

16158

AN:

41482

American (AMR)

AF:

0.661

AC:

10112

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2147

AN:

3472

East Asian (EAS)

AF:

0.456

AC:

2356

AN:

5164

South Asian (SAS)

AF:

0.490

AC:

2366

AN:

4830

European-Finnish (FIN)

AF:

0.530

AC:

5577

AN:

10518

Middle Eastern (MID)

AF:

0.507

AC:

148

AN:

292

European-Non Finnish (NFE)

AF:

0.621

AC:

42177

AN:

67972

Other (OTH)

AF:

0.567

AC:

1197

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1893

3786

5678

7571

9464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.77

PhyloP100

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over