dbSNP rs587555: NFKBIZ:c.430-32A>G (chr3-101852706-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031419.4(NFKBIZ):c.430-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,532,600 control chromosomes in the GnomAD database, including 322,054 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.57 ( 25670 hom., cov: 32)

Exomes 𝑓: 0.65 ( 296384 hom. )

Consequence

NFKBIZ
NM_031419.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIZ	NM_031419.4 link	c.430-32A>G		intron_variant	Intron 2 of 11	ENST00000326172.9	NP_113607.1	Q9BYH8-1
NFKBIZ	NM_001005474.3 link	c.130-32A>G		intron_variant	Intron 3 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.430-32A>G		intron_variant	Intron 2 of 11	1	NM_031419.4	ENSP00000325663.5		Q9BYH8-1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86343

AN:

151942

Hom.:

25651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.617

AC:

146567

AN:

237664

Hom.:

46533

AF XY:

0.614

AC XY:

78879

AN XY:

128446

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.754

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.484

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.651

AC:

898175

AN:

1380538

Hom.:

296384

Cov.:

AF XY:

0.646

AC XY:

446508

AN XY:

690728

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.744

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.568

AC:

86414

AN:

152062

Hom.:

25670

Cov.:

AF XY:

0.561

AC XY:

41719

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.397

Gnomad4 AMR

AF:

0.676

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.512

Gnomad4 FIN

AF:

0.546

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.603

Hom.:

5142

Bravo

AF:

0.578

Asia WGS

AF:

0.473

AC:

1646

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

0.80

DANN

Benign

0.69

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over