Variant 19-10682618-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017620.3(ILF3):c.1462G>A(p.Ala488Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ILF3
NM_017620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.285

Variant links:

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]

ILF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013191849).

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILF3	NM_017620.3 linkuse as main transcript	c.1462G>A	p.Ala488Thr	missense_variant	13/20	ENST00000588657.6	NP_060090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6 linkuse as main transcript	c.1462G>A	p.Ala488Thr	missense_variant	13/20	5	NM_017620.3	ENSP00000468181	P3	Q12906-7

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

250792

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461528

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000223

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000295

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.1462G>A (p.A488T) alteration is located in exon 13 (coding exon 12) of the ILF3 gene. This alteration results from a G to A substitution at nucleotide position 1462, causing the alanine (A) at amino acid position 488 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.3

DANN

Benign

0.77

DEOGEN2

Benign

0.14

.;.;.;.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.86

D;D;D;D;D;.;D

M_CAP

Benign

0.0027

MetaRNN

Benign

0.013

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.060

N;N;.;N;.;.;.

REVEL

Benign

0.067

Sift

Benign

0.37

T;T;.;T;.;.;.

Sift4G

Benign

0.23

T;T;T;T;T;T;T

Polyphen

0.0010, 0.0, 0.0030

.;B;B;B;B;.;B

Vest4

0.082

MVP

0.24

MPC

0.31

ClinPred

0.023

GERP RS

-5.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.029

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over