chr19-10671042-A-C

Position:

• chr19-10671042-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017620.3(ILF3):​c.72A>C​(p.Thr24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,614,206 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (2 hom.)
• Consequence: ILF3 NM_017620.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-10671042-A-C is Benign according to our data. Variant chr19-10671042-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BS2: High AC in GnomAd4 at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILF3	NM_017620.3	c.72A>C	p.Thr24=	synonymous_variant	3/20	ENST00000588657.6	NP_060090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6	c.72A>C	p.Thr24=	synonymous_variant	3/20	5	NM_017620.3	ENSP00000468181	P3

Frequencies

GnomAD3 genomes AF: 0.000768 AC: 117 AN: 152264 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000979 AC: 246 AN: 251236 Hom.: 0 AF XY: 0.000950 AC XY: 129 AN XY: 135804

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000894 AC: 1307 AN: 1461824 Hom.: 2 Cov.: 31 AF XY: 0.000914 AC XY: 665 AN XY: 727208

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00100

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.000768 AC: 117 AN: 152382 Hom.: 0 Cov.: 32 AF XY: 0.000805 AC XY: 60 AN XY: 74518

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000805

EpiCase AF: 0.00191

EpiControl AF: 0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

ILF3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140639398; hg19: chr19-10781718;