rs2569512

Positions:

• chr19-10679486-T-C

Variant summary

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

The NM_017620.3(ILF3):​c.747+294T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,500 control chromosomes in the GnomAD database, including 44,051 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 0.76 (44051 hom., cov: 30)
• Consequence: ILF3 NM_017620.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

Genes affected

ILF3 (HGNC:6038): (interleukin enhancer binding factor 3) This gene encodes a double-stranded RNA (dsRNA) binding protein that complexes with other proteins, dsRNAs, small noncoding RNAs, and mRNAs to regulate gene expression and stabilize mRNAs. This protein (NF90, ILF3) forms a heterodimer with a 45 kDa transcription factor (NF45, ILF2) required for T-cell expression of interleukin 2. This complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. In contrast, an isoform (NF110) of this gene that is predominantly restricted to the nucleus has only minor effects on cell growth when its levels are reduced. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILF3	NM_017620.3	c.747+294T>C		intron_variant		ENST00000588657.6	NP_060090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6	c.747+294T>C		intron_variant		5	NM_017620.3	ENSP00000468181	P3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114319 AN: 151382 Hom.: 44001 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.755 AC: 114425 AN: 151500 Hom.: 44051 Cov.: 30 AF XY: 0.758 AC XY: 56106 AN XY: 74016

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.729

Alfa AF: 0.754 Hom.: 9032

Bravo AF: 0.761

Asia WGS AF: 0.762 AC: 2646 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.41

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: rs2569512; hg19: chr19-10790162; COSMIC: COSV51558172; COSMIC: COSV51558172;