rs772246240

Variant names:

• chr6-44265366-C-G
• rs772246240
• ENST00000275015.9:c.398G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-44265366-C-G
• chr6-44265366-C-T

Variant summary

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

The ENST00000275015.9(NFKBIE):​c.398G>C​(p.Arg133Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R133Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NFKBIE ENST00000275015.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=0.09201074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIE	NM_004556.3	c.-20G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000619360.6	NP_004547.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIE	ENST00000275015.9	c.398G>C	p.Arg133Pro	missense_variant	Exon 1 of 6	1		ENSP00000275015.3
NFKBIE	ENST00000619360.6	c.-20G>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_004556.3	ENSP00000480216.1
NFKBIE	ENST00000477930.2	n.-20G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000454778.2
NFKBIE	ENST00000477930.2	n.-20G>C		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000454778.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 2 AN: 166188 Hom.: 0 AF XY: 0.0000218 AC XY: 2 AN XY: 91560

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: 0.00

Gnomad NFE exome AF: 0.0000287

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1408600 Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 2 AN XY: 697556

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: 0.00000275

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	0.081
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.61
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.26
Sift	Benign	0.52	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.0	B
Vest4		0.15
MutPred		0.33		Loss of MoRF binding (P = 0.0068);
MVP		0.78
MPC		1.1
ClinPred		0.055	T
GERP RS		-3.5
Varity_R		0.10
gMVP		0.093

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: rs772246240; hg19: chr6-44233103;