Variant 3-101857058-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_031419.4(NFKBIZ):c.1825-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,539,284 control chromosomes in the GnomAD database, including 600 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 0.020 ( 52 hom., cov: 31)

Exomes 𝑓: 0.022 ( 548 hom. )

Consequence

NFKBIZ
NM_031419.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.411

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

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0196 (2955/150706) while in subpopulation NFE AF= 0.0259 (1755/67692). AF 95% confidence interval is 0.0249. There are 52 homozygotes in gnomad4. There are 1547 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2955 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIZ	NM_031419.4 linkuse as main transcript	c.1825-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000326172.9
NFKBIZ	NM_001005474.3 linkuse as main transcript	c.1525-15C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIZ	ENST00000326172.9 linkuse as main transcript	c.1825-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031419.4	P4	Q9BYH8-1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2955

AN:

150590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00626

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0164

GnomAD3 exomes

AF:

0.0208

AC:

4859

AN:

233430

Hom.:

127

AF XY:

0.0209

AC XY:

2638

AN XY:

126452

show subpopulations

Gnomad AFR exome

AF:

0.00341

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.000238

Gnomad SAS exome

AF:

0.00605

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0217

GnomAD4 exome

AF:

0.0225

AC:

31217

AN:

1388578

Hom.:

548

Cov.:

AF XY:

0.0220

AC XY:

15171

AN XY:

690548

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.0000515

Gnomad4 SAS exome

AF:

0.00633

Gnomad4 FIN exome

AF:

0.0797

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0196

AC:

2955

AN:

150706

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

1547

AN XY:

73438

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00981

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00627

Gnomad4 FIN

AF:

0.0840

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0162

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.67

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