6-31558259-C-T

Variant names:

• chr6-31558259-C-T
• rs752392625
• NM_005007.4:c.794C>T

Variant summary

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

The NM_005007.4(NFKBIL1):​c.794C>T​(p.Ala265Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000764 in 1,439,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

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=0.058377564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.794C>T	p.Ala265Val	missense_variant	Exon 4 of 4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.749C>T	p.Ala250Val	missense_variant	Exon 4 of 4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.725C>T	p.Ala242Val	missense_variant	Exon 4 of 4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.680C>T	p.Ala227Val	missense_variant	Exon 4 of 4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.794C>T	p.Ala265Val	missense_variant	Exon 4 of 4	1	NM_005007.4	ENSP00000365318.4
NFKBIL1	ENST00000376145.8	c.749C>T	p.Ala250Val	missense_variant	Exon 4 of 4	1		ENSP00000365315.4
NFKBIL1	ENST00000376146.8	c.725C>T	p.Ala242Val	missense_variant	Exon 4 of 4	4		ENSP00000365316.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000764 AC: 11 AN: 1439852 Hom.: 0 Cov.: 35 AF XY: 0.00000841 AC XY: 6 AN XY: 713698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000999

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000855 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rheumatoid arthritis Uncertain:1

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;.;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.093
MutPred		0.34		.;Gain of helix (P = 0.027);.;
MVP		0.26
MPC		0.61
ClinPred		0.11	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.54

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: rs752392625; hg19: chr6-31526036;