chr19-39244853-T-C

Variant summary

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

The NM_172139.4(IFNL3):ā€‹c.115A>Gā€‹(p.Ile39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,808 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

IFNL3
NM_172139.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.714
Variant links:
Genes affected
IFNL3 (HGNC:18365): (interferon lambda 3) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008]

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=0.05866465).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFNL3NM_172139.4 linkuse as main transcriptc.115A>G p.Ile39Val missense_variant 1/5 ENST00000413851.3 NP_742151.2 Q8IZI9A0A7R8C2Z6
IFNL3NM_001346937.2 linkuse as main transcriptc.127A>G p.Ile43Val missense_variant 2/6 NP_001333866.1 Q8IZI9A0A0C4DGW8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IFNL3ENST00000413851.3 linkuse as main transcriptc.115A>G p.Ile39Val missense_variant 1/51 NM_172139.4 ENSP00000409000.2 Q8IZI9
IFNL3ENST00000613087.5 linkuse as main transcriptc.127A>G p.Ile43Val missense_variant 2/61 ENSP00000481633.1 A0A0C4DGW8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251056
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135700
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461658
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000113
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsOct 12, 2024The c.115A>G (p.I39V) alteration is located in exon 1 (coding exon 1) of the IFNL3 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the isoleucine (I) at amino acid position 39 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
2.0
DANN
Benign
0.91
DEOGEN2
Benign
0.0066
.;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
.;L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.44
.;N
REVEL
Benign
0.024
Sift
Benign
0.18
.;T
Sift4G
Benign
0.17
T;T
Polyphen
0.0010
.;B
Vest4
0.12
MutPred
0.23
.;Gain of disorder (P = 0.094);
MVP
0.092
MPC
0.16
ClinPred
0.015
T
GERP RS
0.67
Varity_R
0.12
gMVP
0.10

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.

Other links and lift over

dbSNP: rs202115118; hg19: chr19-39735493; API