6-31558344-C-G

Position:

• chr6-31558344-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005007.4(NFKBIL1):​c.879C>G​(p.Ser293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.529

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]

ACMG classification

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=0.06978181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_005007.4	c.879C>G	p.Ser293Arg	missense_variant	4/4	ENST00000376148.9
NFKBIL1	NM_001144961.2	c.834C>G	p.Ser278Arg	missense_variant	4/4
NFKBIL1	NM_001144962.2	c.810C>G	p.Ser270Arg	missense_variant	4/4
NFKBIL1	NM_001144963.2	c.765C>G	p.Ser255Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.879C>G	p.Ser293Arg	missense_variant	4/4	1	NM_005007.4	P4
NFKBIL1	ENST00000376145.8	c.834C>G	p.Ser278Arg	missense_variant	4/4	1
NFKBIL1	ENST00000376146.8	c.810C>G	p.Ser270Arg	missense_variant	4/4	4		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.879C>G (p.S293R) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a C to G substitution at nucleotide position 879, causing the serine (S) at amino acid position 293 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0090	T;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.64	T;.;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.78	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.46	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.10
MutPred		0.36		.;Loss of phosphorylation at S293 (P = 0.0115);.;
MVP		0.12
MPC		0.69
ClinPred		0.21	T
GERP RS		-0.99
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31526121;