rs755202910

Variant names:

• chr6-44265087-C-A
• rs755202910
• NM_004556.3:c.260G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-44265087-C-A
• chr6-44265087-C-G
• chr6-44265087-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004556.3(NFKBIE):​c.260G>T​(p.Gly87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,559,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: NFKBIE NM_004556.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.215
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034487814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004556.3. 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
	NFKBIE	NM_004556.3	MANE Select	c.260G>T	p.Gly87Val	missense	Exon 1 of 6	NP_004547.3	Q7LC14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIE	ENST00000619360.6	TSL:1 MANE Select	c.260G>T	p.Gly87Val	missense	Exon 1 of 6	ENSP00000480216.1	Q7LC14
	NFKBIE	ENST00000275015.9	TSL:1	c.677G>T	p.Gly226Val	missense	Exon 1 of 6	ENSP00000275015.3	O00221
	NFKBIE	ENST00000890578.1		c.260G>T	p.Gly87Val	missense	Exon 1 of 6	ENSP00000560637.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152060 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000166 AC: 27 AN: 162984 AF XY: 0.000174

Gnomad AFR exome AF: 0.000103

Gnomad AMR exome AF: 0.000201

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 165 AN: 1406966 Hom.: 0 Cov.: 32 AF XY: 0.000118 AC XY: 82 AN XY: 694430

African (AFR) AF: 0.0000920 AC: 3 AN: 32608

American (AMR) AF: 0.000139 AC: 5 AN: 35994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37220

South Asian (SAS) AF: 0.00 AC: 0 AN: 79964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000143 AC: 155 AN: 1082478

Other (OTH) AF: 0.0000171 AC: 1 AN: 58322

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74392

African (AFR) AF: 0.000144 AC: 6 AN: 41558

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000135 Hom.: 0

ExAC AF: 0.0000726 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.21
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.063
Sift	Benign	0.096	T
Sift4G	Benign	0.30	T
Polyphen		0.022	B
Vest4		0.084
MVP		0.56
MPC		0.96
ClinPred		0.018	T
GERP RS		-2.0
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.28
Mutation Taster		=99/1	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: rs755202910; hg19: chr6-44232824;