dbSNP rs200454925: NFKBIL1:p.Asp115Asn (chr6-31557636-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005007.4(NFKBIL1):c.343G>A(p.Asp115Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000152 in 1,529,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Publications

0 publications found

Variant links:

Genes affected

NFKBIL1 (HGNC:7800): (NFKB inhibitor like 1) This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

NFKBIL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18557781).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005007.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFKBIL1	NM_005007.4	MANE Select	c.343G>A	p.Asp115Asn	missense	Exon 3 of 4	NP_004998.3
NFKBIL1	NM_001144961.2		c.343G>A	p.Asp115Asn	missense	Exon 3 of 4	NP_001138433.1	A0A0A0MRT5
NFKBIL1	NM_001144962.2		c.274G>A	p.Asp92Asn	missense	Exon 3 of 4	NP_001138434.1	Q5STV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.343G>A	p.Asp115Asn	missense	Exon 3 of 4	ENSP00000365318.4	Q9UBC1-1
NFKBIL1	ENST00000376145.8	TSL:1	c.343G>A	p.Asp115Asn	missense	Exon 3 of 4	ENSP00000365315.4	A0A0A0MRT5
NFKBIL1	ENST00000376146.8	TSL:4	c.274G>A	p.Asp92Asn	missense	Exon 3 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000206

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000129

AC:

AN:

201462

AF XY:

0.000102

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.0000760

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.000154

AC:

212

AN:

1377430

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

108

AN XY:

675344

show subpopulations

African (AFR)

AF:

0.0000641

AC:

AN:

31192

American (AMR)

AF:

0.000140

AC:

AN:

35598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21840

East Asian (EAS)

AF:

0.00

AC:

AN:

37830

South Asian (SAS)

AF:

0.0000411

AC:

AN:

72926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51086

Middle Eastern (MID)

AF:

0.000202

AC:

AN:

4944

European-Non Finnish (NFE)

AF:

0.000183

AC:

195

AN:

1065362

Other (OTH)

AF:

0.000106

AC:

AN:

56652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.000131

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41416

American (AMR)

AF:

0.000196

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68036

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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:

0.000217

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000115

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

Uncertain

0.34

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.024

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.78

PhyloP100

5.6

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.5

REVEL

Benign

0.23

Sift

Benign

0.17

Sift4G

Benign

0.14

Polyphen

0.91

Vest4

0.26

MVP

0.46

MPC

1.2

ClinPred

0.11

GERP RS

5.9

gMVP

0.53

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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