6-31558085-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005007.4(NFKBIL1):c.620G>A(p.Arg207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000555 in 1,477,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.976

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03242472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4 link	c.620G>A	p.Arg207Gln	missense_variant	Exon 4 of 4	ENST00000376148.9	NP_004998.3	Q9UBC1-1A8K778
NFKBIL1	NM_001144961.2 link	c.575G>A	p.Arg192Gln	missense_variant	Exon 4 of 4		NP_001138433.1	Q9UBC1-3A0A0A0MRT5A8K778
NFKBIL1	NM_001144962.2 link	c.551G>A	p.Arg184Gln	missense_variant	Exon 4 of 4		NP_001138434.1	Q9UBC1-2Q5STV6
NFKBIL1	NM_001144963.2 link	c.506G>A	p.Arg169Gln	missense_variant	Exon 4 of 4		NP_001138435.1	Q9UBC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NFKBIL1	ENST00000376148.9 link	c.620G>A	p.Arg207Gln	missense_variant	Exon 4 of 4	1	NM_005007.4	ENSP00000365318.4	Q9UBC1-1
NFKBIL1	ENST00000376145.8 link	c.575G>A	p.Arg192Gln	missense_variant	Exon 4 of 4	1		ENSP00000365315.4	Q9UBC1-3A0A0A0MRT5
NFKBIL1	ENST00000376146.8 link	c.551G>A	p.Arg184Gln	missense_variant	Exon 4 of 4	4		ENSP00000365316.4	Q9UBC1-2Q5STV6
NFKBIL1	ENST00000473655.1 link	n.*126G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000675

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000220

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000903

AC:

AN:

243712

Hom.:

AF XY:

0.0000901

AC XY:

AN XY:

133212

show subpopulations

Gnomad AFR exome

AF:

0.0000670

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.000712

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1330670

Hom.:

Cov.:

AF XY:

0.0000576

AC XY:

AN XY:

660260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000677

Gnomad4 AMR exome

AF:

0.0000985

Gnomad4 ASJ exome

AF:

0.000140

Gnomad4 EAS exome

AF:

0.000436

Gnomad4 SAS exome

AF:

0.0000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000447

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.0000204

AC:

AN:

146976

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

71614

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000675

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000220

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000891

Hom.:

ExAC

AF:

0.0000840

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.620G>A (p.R207Q) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a G to A substitution at nucleotide position 620, causing the arginine (R) at amino acid position 207 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.91

N;N;N

REVEL

Benign

0.034

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.097

MutPred

0.28

.;Loss of loop (P = 9e-04);.;

MVP

0.24

MPC

0.71

ClinPred

0.036

GERP RS

0.33

gMVP

0.31

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