6-31557780-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005007.4(NFKBIL1):c.487C>G(p.Arg163Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,090 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.155

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 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=0.051853716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_005007.4	c.487C>G	p.Arg163Gly	missense_variant	3/4	ENST00000376148.9
NFKBIL1	NM_001144961.2	c.487C>G	p.Arg163Gly	missense_variant	3/4
NFKBIL1	NM_001144962.2	c.418C>G	p.Arg140Gly	missense_variant	3/4
NFKBIL1	NM_001144963.2	c.418C>G	p.Arg140Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.487C>G	p.Arg163Gly	missense_variant	3/4	1	NM_005007.4	P4
NFKBIL1	ENST00000376145.8	c.487C>G	p.Arg163Gly	missense_variant	3/4	1
NFKBIL1	ENST00000376146.8	c.418C>G	p.Arg140Gly	missense_variant	3/4	4		A1
NFKBIL1	ENST00000473655.1	n.521C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460090 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726134

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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

Dec 16, 2023

The c.487C>G (p.R163G) alteration is located in exon 3 (coding exon 3) of the NFKBIL1 gene. This alteration results from a C to G substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 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	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Uncertain	0.97
DEOGEN2	Benign	0.034	T;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.73	T;.;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.046	D;D;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.22
MutPred		0.34		.;Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.10
MPC		1.1
ClinPred		0.11	T
GERP RS		2.5
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: chr6-31525557;