chr19-10679486-T-C

Variant names:

• chr19-10679486-T-C
• rs2569512
• NM_017620.3:c.747+294T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILF3	NM_017620.3	MANE Select	c.747+294T>C		intron	N/A	NP_060090.2
	ILF3	NM_001394808.1		c.747+294T>C		intron	N/A	NP_001381737.1	Q12906-7
	ILF3	NM_001394809.1		c.747+294T>C		intron	N/A	NP_001381738.1	Q12906-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILF3	ENST00000588657.6	TSL:5 MANE Select	c.747+294T>C		intron	N/A	ENSP00000468181.1	Q12906-7
	ILF3	ENST00000407004.8	TSL:1	c.747+294T>C		intron	N/A	ENSP00000384660.2	Q12906-6
	ILF3	ENST00000250241.12	TSL:1	c.747+294T>C		intron	N/A	ENSP00000250241.8	Q12906-5

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

African (AFR) AF: 0.906 AC: 37452 AN: 41336

American (AMR) AF: 0.768 AC: 11699 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2479 AN: 3460

East Asian (EAS) AF: 0.678 AC: 3484 AN: 5138

South Asian (SAS) AF: 0.765 AC: 3678 AN: 4810

European-Finnish (FIN) AF: 0.724 AC: 7567 AN: 10456

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 45936 AN: 67766

Other (OTH) AF: 0.729 AC: 1529 AN: 2096

Alfa AF: 0.758 Hom.: 9343

Bravo AF: 0.761

Asia WGS AF: 0.762 AC: 2646 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.41
PhyloP100		-0.35
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: rs2569512; hg19: chr19-10790162; COSMIC: COSV51558172; COSMIC: COSV51558172;