Genetic Variant NFKBIL1:p.Arg251Gln (chr6-31558217-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005007.4(NFKBIL1):c.752G>A(p.Arg251Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,597,688 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.509

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024567246).

BP6

Variant 6-31558217-G-A is Benign according to our data. Variant chr6-31558217-G-A is described in ClinVar as Benign. ClinVar VariationId is 3034111.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

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.752G>A	p.Arg251Gln	missense	Exon 4 of 4	NP_004998.3
NFKBIL1	NM_001144961.2		c.707G>A	p.Arg236Gln	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
NFKBIL1	NM_001144962.2		c.683G>A	p.Arg228Gln	missense	Exon 4 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.752G>A	p.Arg251Gln	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
NFKBIL1	ENST00000376145.8	TSL:1	c.707G>A	p.Arg236Gln	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
NFKBIL1	ENST00000376146.8	TSL:4	c.683G>A	p.Arg228Gln	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00228

AC:

479

AN:

210474

AF XY:

0.00221

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.000745

GnomAD4 exome

AF:

0.00112

AC:

1618

AN:

1445340

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

755

AN XY:

717308

show subpopulations

African (AFR)

AF:

0.000330

AC:

AN:

33368

American (AMR)

AF:

0.000241

AC:

AN:

41510

Ashkenazi Jewish (ASJ)

AF:

0.0000389

AC:

AN:

25704

East Asian (EAS)

AF:

0.0000765

AC:

AN:

39228

South Asian (SAS)

AF:

0.0000476

AC:

AN:

83982

European-Finnish (FIN)

AF:

0.0190

AC:

970

AN:

51030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.000515

AC:

569

AN:

1104936

Other (OTH)

AF:

0.000835

AC:

AN:

59866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

101

202

302

403

504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.00220

AC:

335

AN:

152348

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41578

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0253

AC:

269

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000771

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000332

AC:

ESP6500EA

AF:

0.000370

AC:

ExAC

AF:

0.00171

AC:

201

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NFKBIL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

PhyloP100

0.51

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.044

Sift

Benign

0.23

Sift4G

Benign

0.11

Polyphen

0.0060

Vest4

0.060

MVP

0.26

MPC

0.71

ClinPred

0.015

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.35

Mutation Taster

=99/1

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