rs201365412

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000572.3(IL10):​c.371G>T​(p.Arg124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL10
NM_000572.3 missense

Scores

1
12
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.677
Variant links:
Genes affected
IL10 (HGNC:5962): (interleukin 10) The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]
IL19 (HGNC:5990): (interleukin 19) The protein encoded by this gene is a cytokine that belongs to the IL10 cytokine subfamily. This cytokine is found to be preferentially expressed in monocytes. It can bind the IL20 receptor complex and lead to the activation of the signal transducer and activator of transcription 3 (STAT3). A similar cytokine in mouse is reported to up-regulate the expression of IL6 and TNF-alpha and induce apoptosis, which suggests a role of this cytokine in inflammatory responses. Alternatively spliced transcript variants encoding the distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL10NM_000572.3 linkc.371G>T p.Arg124Leu missense_variant Exon 3 of 5 ENST00000423557.1 NP_000563.1 P22301Q6FGW4
IL19NM_153758.5 linkc.-313C>A 5_prime_UTR_variant Exon 1 of 7 ENST00000659997.3 NP_715639.2 Q9UHD0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL10ENST00000423557.1 linkc.371G>T p.Arg124Leu missense_variant Exon 3 of 5 1 NM_000572.3 ENSP00000412237.1 P22301
IL19ENST00000659997 linkc.-313C>A 5_prime_UTR_variant Exon 1 of 7 NM_153758.5 ENSP00000499459.2 Q9UHD0-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461790
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Uncertain
0.015
D
MutationAssessor
Pathogenic
3.2
M;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.8
N;.
REVEL
Uncertain
0.48
Sift
Uncertain
0.026
D;.
Sift4G
Uncertain
0.011
D;.
Polyphen
1.0
D;.
Vest4
0.48
MutPred
0.73
Loss of MoRF binding (P = 0.0123);.;
MVP
0.91
MPC
0.52
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.52
gMVP
0.46

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: rs201365412; hg19: chr1-206944259; API