6-31558190-A-C

Variant names:

• chr6-31558190-A-C
• NM_005007.4:c.725A>C

Variant summary

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

The NM_005007.4(NFKBIL1):​c.725A>C​(p.Glu242Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,468 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.

• 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: 5.45

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=0.14466372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.725A>C	p.Glu242Ala	missense_variant	Exon 4 of 4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.680A>C	p.Glu227Ala	missense_variant	Exon 4 of 4		NP_001138433.1
NFKBIL1	NM_001144962.2	c.656A>C	p.Glu219Ala	missense_variant	Exon 4 of 4		NP_001138434.1
NFKBIL1	NM_001144963.2	c.611A>C	p.Glu204Ala	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.725A>C	p.Glu242Ala	missense_variant	Exon 4 of 4	1	NM_005007.4	ENSP00000365318.4
NFKBIL1	ENST00000376145.8	c.680A>C	p.Glu227Ala	missense_variant	Exon 4 of 4	1		ENSP00000365315.4
NFKBIL1	ENST00000376146.8	c.656A>C	p.Glu219Ala	missense_variant	Exon 4 of 4	4		ENSP00000365316.4
NFKBIL1	ENST00000473655.1	n.*231A>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455468 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 723524

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.;T
Eigen	Benign	0.092
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T;.;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.88	P;.;.
Vest4		0.26
MutPred		0.36		.;Loss of helix (P = 0.0167);.;
MVP		0.23
MPC		1.7
ClinPred		0.75	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31525967;