Variant 6-31558190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005007.4(NFKBIL1):c.725A>G(p.Glu242Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,607,634 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 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14539734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NFKBIL1	NM_005007.4 linkuse as main transcript	c.725A>G	p.Glu242Gly	missense_variant	4/4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2 linkuse as main transcript	c.680A>G	p.Glu227Gly	missense_variant	4/4		NP_001138433.1
NFKBIL1	NM_001144962.2 linkuse as main transcript	c.656A>G	p.Glu219Gly	missense_variant	4/4		NP_001138434.1
NFKBIL1	NM_001144963.2 linkuse as main transcript	c.611A>G	p.Glu204Gly	missense_variant	4/4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 linkuse as main transcript	c.725A>G	p.Glu242Gly	missense_variant	4/4	1	NM_005007.4	ENSP00000365318	P4	Q9UBC1-1
NFKBIL1	ENST00000376145.8 linkuse as main transcript	c.680A>G	p.Glu227Gly	missense_variant	4/4	1		ENSP00000365315		Q9UBC1-3
NFKBIL1	ENST00000376146.8 linkuse as main transcript	c.656A>G	p.Glu219Gly	missense_variant	4/4	4		ENSP00000365316	A1	Q9UBC1-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000261

AC:

AN:

230220

Hom.:

AF XY:

0.0000238

AC XY:

AN XY:

126230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000590

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1455468

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

723524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000620

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.725A>G (p.E242G) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a A to G substitution at nucleotide position 725, causing the glutamic acid (E) at amino acid position 242 to be replaced by a glycine (G). 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

0.26

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

T;.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.5

D;D;N

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D;T

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.96

D;.;.

Vest4

0.26

MVP

0.23

MPC

1.7

ClinPred

0.51

GERP RS

6.1

gMVP

0.70

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