6-44265336-G-T

Variant names:

• chr6-44265336-G-T
• rs769415987
• NM_004556.3:c.11C>A

Variant summary

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

The NM_004556.3(NFKBIE):​c.11C>A​(p.Ala4Glu) 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. 13/21 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFKBIE NM_004556.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

NFKBIE (HGNC:7799): (NFKB inhibitor epsilon) The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus. [provided by RefSeq, Sep 2011]

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=0.16082552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIE	NM_004556.3	c.11C>A	p.Ala4Glu	missense_variant	Exon 1 of 6	ENST00000619360.6	NP_004547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIE	ENST00000619360.6	c.11C>A	p.Ala4Glu	missense_variant	Exon 1 of 6	1	NM_004556.3	ENSP00000480216.1
NFKBIE	ENST00000275015.9	c.428C>A	p.Ala143Glu	missense_variant	Exon 1 of 6	1		ENSP00000275015.3
NFKBIE	ENST00000477930.2	n.11C>A		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000454778.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000625 AC: 1 AN: 160066 Hom.: 0 AF XY: 0.0000114 AC XY: 1 AN XY: 87386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000110

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402308 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 693464

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.28	.;N
REVEL	Benign	0.17
Sift	Benign	0.21	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.93	.;P
Vest4		0.33
MutPred		0.21		.;Loss of MoRF binding (P = 0.0517);
MVP		0.78
MPC		1.4
ClinPred		0.88	D
GERP RS		3.1
Varity_R		0.090
gMVP		0.17

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: rs769415987; hg19: chr6-44233073;