19-10688228-G-A

Variant names:

• chr19-10688228-G-A
• rs2569507
• NM_017620.3:c.2435-322G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017620.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILF3	NM_017620.3	MANE Select	c.2435-322G>A		intron	N/A	NP_060090.2
	ILF3	NM_001394808.1		c.2435-322G>A		intron	N/A	NP_001381737.1
	ILF3	NM_001394809.1		c.2435-322G>A		intron	N/A	NP_001381738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILF3	ENST00000588657.6	TSL:5 MANE Select	c.2435-322G>A		intron	N/A	ENSP00000468181.1
	ILF3	ENST00000586544.1	TSL:1	n.510+114G>A		intron	N/A
	ILF3	ENST00000590261.5	TSL:5	c.2423-322G>A		intron	N/A	ENSP00000468156.1

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

African (AFR) AF: 0.283 AC: 1165 AN: 4110

American (AMR) AF: 0.539 AC: 2634 AN: 4888

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 2511 AN: 4954

East Asian (EAS) AF: 0.246 AC: 2514 AN: 10210

South Asian (SAS) AF: 0.536 AC: 1374 AN: 2562

European-Finnish (FIN) AF: 0.462 AC: 3619 AN: 7838

Middle Eastern (MID) AF: 0.405 AC: 276 AN: 682

European-Non Finnish (NFE) AF: 0.488 AC: 39112 AN: 80074

Other (OTH) AF: 0.469 AC: 3966 AN: 8460

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

African (AFR) AF: 0.300 AC: 12411 AN: 41412

American (AMR) AF: 0.517 AC: 7905 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1640 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2718 AN: 4818

European-Finnish (FIN) AF: 0.455 AC: 4802 AN: 10552

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34104 AN: 67936

Other (OTH) AF: 0.436 AC: 921 AN: 2114

Alfa AF: 0.473 Hom.: 18140

Bravo AF: 0.431

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.27
PhyloP100		-3.2
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: rs2569507; hg19: chr19-10798904; COSMIC: COSV51561187; COSMIC: COSV51561187;