Variant 6-31558297-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.832A>G(p.Arg278Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000007 in 1,429,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: not found (cov: 31)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

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:

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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=0.17850387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_005007.4 linkuse as main transcript	c.832A>G	p.Arg278Gly	missense_variant	4/4	ENST00000376148.9	NP_004998.3	Q9UBC1-1A8K778
NFKBIL1	NM_001144961.2 linkuse as main transcript	c.787A>G	p.Arg263Gly	missense_variant	4/4		NP_001138433.1	Q9UBC1-3A0A0A0MRT5A8K778
NFKBIL1	NM_001144962.2 linkuse as main transcript	c.763A>G	p.Arg255Gly	missense_variant	4/4		NP_001138434.1	Q9UBC1-2Q5STV6
NFKBIL1	NM_001144963.2 linkuse as main transcript	c.718A>G	p.Arg240Gly	missense_variant	4/4		NP_001138435.1	Q9UBC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NFKBIL1	ENST00000376148.9 linkuse as main transcript	c.832A>G	p.Arg278Gly	missense_variant	4/4	1	NM_005007.4	ENSP00000365318.4	Q9UBC1-1
NFKBIL1	ENST00000376145.8 linkuse as main transcript	c.787A>G	p.Arg263Gly	missense_variant	4/4	1		ENSP00000365315.4	Q9UBC1-3A0A0A0MRT5
NFKBIL1	ENST00000376146.8 linkuse as main transcript	c.763A>G	p.Arg255Gly	missense_variant	4/4	4		ENSP00000365316.4	Q9UBC1-2Q5STV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

197358

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

107892

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000700

AC:

AN:

1429462

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

707758

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000913

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000859

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

Oct 29, 2024

The c.832A>G (p.R278G) 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 832, causing the arginine (R) at amino acid position 278 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

0.058

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.063

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.78

T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.016

D;D;D

Sift4G

Uncertain

0.023

D;D;T

Polyphen

0.68

P;.;.

Vest4

0.20

MutPred

0.25

.;Gain of relative solvent accessibility (P = 0.0166);.;

MVP

0.47

MPC

1.2

ClinPred

0.29

GERP RS

4.0

gMVP

0.50

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