6-31558217-G-A

Variant summary

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

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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 0.509

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 made for transcript

Verdict is Benign. Variant got -10 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 id is 3034111.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NFKBIL1	NM_005007.4 linkuse as main transcript	c.752G>A	p.Arg251Gln	missense_variant	4/4	ENST00000376148.9
NFKBIL1	NM_001144961.2 linkuse as main transcript	c.707G>A	p.Arg236Gln	missense_variant	4/4
NFKBIL1	NM_001144962.2 linkuse as main transcript	c.683G>A	p.Arg228Gln	missense_variant	4/4
NFKBIL1	NM_001144963.2 linkuse as main transcript	c.638G>A	p.Arg213Gln	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9 linkuse as main transcript	c.752G>A	p.Arg251Gln	missense_variant	4/4	1	NM_005007.4	P4	Q9UBC1-1
NFKBIL1	ENST00000376145.8 linkuse as main transcript	c.707G>A	p.Arg236Gln	missense_variant	4/4	1			Q9UBC1-3
NFKBIL1	ENST00000376146.8 linkuse as main transcript	c.683G>A	p.Arg228Gln	missense_variant	4/4	4		A1	Q9UBC1-2

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

GnomAD3 exomes

AF:

0.00228

AC:

479

AN:

210474

Hom.:

AF XY:

0.00221

AC XY:

254

AN XY:

115086

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 SAS 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

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000241

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.0000476

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.000515

Gnomad4 OTH exome

AF:

0.000835

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152348

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0253

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000618

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NFKBIL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.74

T;.;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.89

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0060

B;.;.

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

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