chr6-31558344-C-G

Variant names:

• chr6-31558344-C-G
• NM_005007.4:c.879C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/20 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06978181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005007.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	NM_005007.4	MANE Select	c.879C>G	p.Ser293Arg	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.834C>G	p.Ser278Arg	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.810C>G	p.Ser270Arg	missense	Exon 4 of 4	NP_001138434.1	Q5STV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.879C>G	p.Ser293Arg	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.834C>G	p.Ser278Arg	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.810C>G	p.Ser270Arg	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.53
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.059
Sift	Benign	0.39	T
Sift4G	Benign	0.45	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
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr6-31526121;