6-31557759-G-A

Variant names:

• chr6-31557759-G-A
• rs1261697958
• NM_005007.4:c.466G>A

Variant summary

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

The NM_005007.4(NFKBIL1):​c.466G>A​(p.Glu156Lys) 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. 11/19 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: 32)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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=0.100036085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.466G>A	p.Glu156Lys	missense_variant	Exon 3 of 4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.466G>A	p.Glu156Lys	missense_variant	Exon 3 of 4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.397G>A	p.Glu133Lys	missense_variant	Exon 3 of 4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.397G>A	p.Glu133Lys	missense_variant	Exon 3 of 4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.466G>A	p.Glu156Lys	missense_variant	Exon 3 of 4	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.78	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.079	B;.;.
Vest4		0.34
MutPred		0.37		.;Gain of ubiquitination at E156 (P = 0.0039);Gain of ubiquitination at E156 (P = 0.0039);
MVP		0.26
MPC		0.70
ClinPred		0.19	T
GERP RS		4.7
gMVP		0.38

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: rs1261697958; hg19: chr6-31525536; COSMIC: COSV65990517; COSMIC: COSV65990517;