rs3130062

Positions:

• chr6-31558135-C-G
• chr6-31558135-C-T

Variant summary

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

The ENST00000376148.9(NFKBIL1):​c.670C>G​(p.Arg224Gly) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R224C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFKBIL1 ENST00000376148.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=0.048037708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.670C>G	p.Arg224Gly	missense_variant	4/4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.625C>G	p.Arg209Gly	missense_variant	4/4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.601C>G	p.Arg201Gly	missense_variant	4/4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.556C>G	p.Arg186Gly	missense_variant	4/4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.670C>G	p.Arg224Gly	missense_variant	4/4	1	NM_005007.4	ENSP00000365318	P4
NFKBIL1	ENST00000376145.8	c.625C>G	p.Arg209Gly	missense_variant	4/4	1		ENSP00000365315
NFKBIL1	ENST00000376146.8	c.601C>G	p.Arg201Gly	missense_variant	4/4	4		ENSP00000365316	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.049
DANN	Benign	0.72
DEOGEN2	Benign	0.021	T;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.16	T;.;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.064
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.056
MutPred		0.28		Loss of MoRF binding (P = 0.0335);.;.;
MVP		0.14
MPC		0.78
ClinPred		0.15	T
GERP RS		-8.9
gMVP		0.21

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

Other links and lift over

dbSNP: rs3130062; hg19: chr6-31525912;