rs2233437

Variant names:

• chr6-44260425-G-A
• rs2233437
• NM_004556.3:c.780+26C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-44260425-G-A
• chr6-44260425-G-C
• chr6-44260425-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004556.3(NFKBIE):​c.780+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,613,518 control chromosomes in the GnomAD database, including 147,208 homozygotes. 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: 𝑓 0.35 (11255 hom., cov: 32)
  • Exomes 𝑓: 0.43 (135953 hom.)
• Consequence: NFKBIE NM_004556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

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.780+26C>T		intron	N/A	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.780+26C>T		intron	N/A	ENSP00000480216.1	Q7LC14
	NFKBIE	ENST00000275015.9	TSL:1	c.1197+26C>T		intron	N/A	ENSP00000275015.3	O00221
	NFKBIE	ENST00000890578.1		c.780+26C>T		intron	N/A	ENSP00000560637.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53774 AN: 151948 Hom.: 11247 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.427 AC: 107217 AN: 251020 AF XY: 0.428

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.379

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.450

GnomAD4 exome AF: 0.427 AC: 623757 AN: 1461452 Hom.: 135953 Cov.: 38 AF XY: 0.427 AC XY: 310469 AN XY: 727032

African (AFR) AF: 0.110 AC: 3693 AN: 33474

American (AMR) AF: 0.581 AC: 25949 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 11177 AN: 26130

East Asian (EAS) AF: 0.431 AC: 17111 AN: 39694

South Asian (SAS) AF: 0.414 AC: 35680 AN: 86248

European-Finnish (FIN) AF: 0.430 AC: 22958 AN: 53394

Middle Eastern (MID) AF: 0.455 AC: 2619 AN: 5760

European-Non Finnish (NFE) AF: 0.431 AC: 479480 AN: 1111674

Other (OTH) AF: 0.416 AC: 25090 AN: 60380

GnomAD4 genome AF: 0.354 AC: 53787 AN: 152066 Hom.: 11255 Cov.: 32 AF XY: 0.361 AC XY: 26826 AN XY: 74302

African (AFR) AF: 0.127 AC: 5279 AN: 41500

American (AMR) AF: 0.515 AC: 7885 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1410 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1953 AN: 5148

South Asian (SAS) AF: 0.422 AC: 2038 AN: 4828

European-Finnish (FIN) AF: 0.433 AC: 4571 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29238 AN: 67948

Other (OTH) AF: 0.388 AC: 819 AN: 2112

Alfa AF: 0.375 Hom.: 10856

Bravo AF: 0.349

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.39
PhyloP100		-0.80
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2233437; hg19: chr6-44228162; COSMIC: COSV51490299; COSMIC: COSV51490299;