6-31558262-A-C

Variant names:

• chr6-31558262-A-C
• rs777359918
• NM_005007.4:c.797A>C

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.797A>C​(p.Gln266Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,590,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. Q266R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• 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=0.14308158).

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.797A>C	p.Gln266Pro	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.752A>C	p.Gln251Pro	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.728A>C	p.Gln243Pro	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.797A>C	p.Gln266Pro	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.752A>C	p.Gln251Pro	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.728A>C	p.Gln243Pro	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438456 Hom.: 0 Cov.: 35 AF XY: 0.00000281 AC XY: 2 AN XY: 712854

African (AFR) AF: 0.00 AC: 0 AN: 33192

American (AMR) AF: 0.00 AC: 0 AN: 40766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25434

East Asian (EAS) AF: 0.00 AC: 0 AN: 39082

South Asian (SAS) AF: 0.00 AC: 0 AN: 83486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100548

Other (OTH) AF: 0.00 AC: 0 AN: 59498

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.25
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.072
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.022	D
Polyphen		0.14	B
Vest4		0.17
MutPred		0.39		Loss of helix (P = 0.0304)
MVP		0.25
MPC		0.75
ClinPred		0.65	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.76
Mutation Taster		=72/28	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

dbSNP: rs777359918; hg19: chr6-31526039;