dbSNP rs9841857: NFKBIZ:c.-12+1490A>T (chr3-101831178-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 ENST00000394054.6(NFKBIZ):c.-12+1490A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,204 control chromosomes in the GnomAD database, including 3,198 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 0.18 ( 3198 hom., cov: 32)

Consequence

NFKBIZ
ENST00000394054.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.852

Publications

9 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 links:

NXPE3 (HGNC:28238): (neurexophilin and PC-esterase domain family member 3) This gene encodes a member of the neurexophilin family of neuropeptide-like glycoproteins. The encoded protein contains a variable N-terminal domain, a highly conserved neurexophilin and PC-esterase (NXPE) central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein binds alpha neurexins, a group of presynaptic transmembrane receptors that promote adhesion between dendrites and axons. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

NXPE3 links:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIZ	NM_001005474.3 link	c.-12+1490A>T		intron_variant	Intron 2 of 12		NP_001005474.1	Q9BYH8-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NFKBIZ	ENST00000394054.6 link	c.-12+1490A>T	intron_variant	Intron 2 of 12	1	ENSP00000377618.2	Q9BYH8-2
NFKBIZ	ENST00000483180.5 link	c.-12+2994A>T	intron_variant	Intron 1 of 10	5	ENSP00000419800.1	C9JZ23
NXPE3	ENST00000705586.1 link	c.1269+9428A>T	intron_variant	Intron 7 of 7		ENSP00000516140.1	A0A994J7U7
NFKBIZ	ENST00000461724.5 link	c.-738+1490A>T	intron_variant	Intron 2 of 3	5	ENSP00000418502.1	C9J5G8

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27612

AN:

152086

Hom.:

3200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0464

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.181

AC:

27596

AN:

152204

Hom.:

3198

Cov.:

AF XY:

0.181

AC XY:

13473

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0463

AC:

1923

AN:

41564

American (AMR)

AF:

0.152

AC:

2324

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

908

AN:

3464

East Asian (EAS)

AF:

0.134

AC:

693

AN:

5172

South Asian (SAS)

AF:

0.178

AC:

858

AN:

4828

European-Finnish (FIN)

AF:

0.265

AC:

2795

AN:

10564

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17347

AN:

67996

Other (OTH)

AF:

0.196

AC:

415

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1080

2160

3241

4321

5401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.224

Hom.:

541

Bravo

AF:

0.167

Asia WGS

AF:

0.151

AC:

526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.62

PhyloP100

0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over