6-44264337-A-G

Position:

• chr6-44264337-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004556.3(NFKBIE):​c.365+645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,140 control chromosomes in the GnomAD database, including 11,509 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 0.37 (11509 hom., cov: 33)
• Consequence: NFKBIE NM_004556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIE	NM_004556.3	c.365+645T>C		intron_variant		ENST00000619360.6
POLR1C	NM_001318876.2	c.946-177553A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIE	ENST00000619360.6	c.365+645T>C		intron_variant		1	NM_004556.3	P1
NFKBIE	ENST00000275015.9	c.782+645T>C		intron_variant		1
NFKBIE	ENST00000477930.2	c.365+645T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55874 AN: 152022 Hom.: 11505 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55887 AN: 152140 Hom.: 11509 Cov.: 33 AF XY: 0.374 AC XY: 27801 AN XY: 74364

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.409

Alfa AF: 0.427 Hom.: 18780

Bravo AF: 0.366

Asia WGS AF: 0.416 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.3
DANN	Benign	0.63

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: rs730775; hg19: chr6-44232074;