rs2569507

Positions:

• chr19-10688228-G-A
• chr19-10688228-G-C
• chr19-10688228-G-T

Variant summary

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

The NM_017620.3(ILF3):​c.2435-322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 275,726 control chromosomes in the GnomAD database, including 29,225 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 0.44 (15429 hom., cov: 32)
  • Exomes 𝑓: 0.46 (13796 hom.)
• Consequence: ILF3 NM_017620.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILF3	NM_017620.3	c.2435-322G>A		intron_variant		ENST00000588657.6	NP_060090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6	c.2435-322G>A		intron_variant		5	NM_017620.3	ENSP00000468181	P3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66729 AN: 151828 Hom.: 15430 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.462 AC: 57171 AN: 123778 Hom.: 13796 AF XY: 0.464 AC XY: 29031 AN XY: 62534

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.439 AC: 66725 AN: 151948 Hom.: 15429 Cov.: 32 AF XY: 0.440 AC XY: 32710 AN XY: 74258

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.436

Alfa AF: 0.476 Hom.: 14061

Bravo AF: 0.431

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.27

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: rs2569507; hg19: chr19-10798904; COSMIC: COSV51561187; COSMIC: COSV51561187;