dbSNP rs114679096: NFKBIE:p.Asp65Glu (chr6-44265152-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004556.3(NFKBIE):c.195T>A(p.Asp65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000451 in 1,552,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

NFKBIE
NM_004556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.321

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026627988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004556.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIE	NM_004556.3	MANE Select	c.195T>A	p.Asp65Glu	missense	Exon 1 of 6	NP_004547.3	Q7LC14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFKBIE	ENST00000619360.6	TSL:1 MANE Select	c.195T>A	p.Asp65Glu	missense	Exon 1 of 6	ENSP00000480216.1	Q7LC14
NFKBIE	ENST00000275015.9	TSL:1	c.612T>A	p.Asp204Glu	missense	Exon 1 of 6	ENSP00000275015.3	O00221
NFKBIE	ENST00000890578.1		c.195T>A	p.Asp65Glu	missense	Exon 1 of 6	ENSP00000560637.1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

156472

AF XY:

0.0000364

show subpopulations

Gnomad AFR exome

AF:

0.000571

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000243

AC:

AN:

1399704

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690406

show subpopulations

African (AFR)

AF:

0.000948

AC:

AN:

31652

American (AMR)

AF:

0.00

AC:

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35798

South Asian (SAS)

AF:

0.00

AC:

AN:

79258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079108

Other (OTH)

AF:

0.0000690

AC:

AN:

58010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000236

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000356

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.000956

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000111

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.55

M_CAP

Benign

0.0033

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.32

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.86

REVEL

Benign

0.037

Sift

Benign

0.069

Sift4G

Benign

0.26

Polyphen

0.027

Vest4

0.080

MutPred

0.33

Gain of loop (P = 0.0013)

MVP

0.33

MPC

0.78

ClinPred

0.047

GERP RS

-7.2

PromoterAI

0.054

Neutral

(source)

Varity_R

0.093

gMVP

0.095

Mutation Taster

=97/3

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over