Variant 6-44265666-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000275015.9(NFKBIE):c.98C>T(p.Ser33Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0119 in 1,548,384 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 33)

Exomes 𝑓: 0.012 ( 144 hom. )

Consequence

NFKBIE
ENST00000275015.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.12

Variant links:

Genes affected

NFKBIE (HGNC:7799): (NFKB inhibitor epsilon) The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus. [provided by RefSeq, Sep 2011]

NFKBIE links:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006894827).

BP6

Variant 6-44265666-G-A is Benign according to our data. Variant chr6-44265666-G-A is described in ClinVar as [Benign]. Clinvar id is 3024940.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-176224G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIE	ENST00000275015.9 linkuse as main transcript	c.98C>T	p.Ser33Phe	missense_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1519

AN:

151698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00230

Gnomad AMI

AF:

0.0210

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00928

AC:

1362

AN:

146772

Hom.:

AF XY:

0.00868

AC XY:

686

AN XY:

79070

show subpopulations

Gnomad AFR exome

AF:

0.00212

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.000838

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.0121

AC:

16937

AN:

1396576

Hom.:

144

Cov.:

AF XY:

0.0120

AC XY:

8240

AN XY:

688730

show subpopulations

Gnomad4 AFR exome

AF:

0.00235

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.00183

Gnomad4 EAS exome

AF:

0.0000841

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.00912

GnomAD4 genome

AF:

0.0100

AC:

1519

AN:

151808

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

817

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.0374

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00762

ESP6500AA

AF:

0.000929

AC:

ESP6500EA

AF:

0.00377

AC:

ExAC

AF:

0.00260

AC:

165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

NFKBIE: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

Eigen

Benign

0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0069

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.13

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.17

MVP

0.43

MPC

1.4

ClinPred

0.057

GERP RS

4.5

Varity_R

0.12

gMVP

0.029

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over