6-31558217-G-C

Variant names:

• chr6-31558217-G-C
• rs149963082
• NM_005007.4:c.752G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005007.4(NFKBIL1):​c.752G>C​(p.Arg251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R251Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.266573).

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.752G>C	p.Arg251Pro	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.707G>C	p.Arg236Pro	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.683G>C	p.Arg228Pro	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.752G>C	p.Arg251Pro	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.707G>C	p.Arg236Pro	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.683G>C	p.Arg228Pro	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1445342 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 717310

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 41510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 83982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51030

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104938

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.51
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.022	D
Polyphen		0.61	P
Vest4		0.33
MutPred		0.43		Gain of loop (P = 0)
MVP		0.60
MPC		1.5
ClinPred		0.92	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.84
Mutation Taster		=73/27	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: rs149963082; hg19: chr6-31525994;