GeneBe

1-206770623-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000572.3(IL10):​c.378+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 320,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

IL10
NM_000572.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.737

Publications

104 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IL10
NM_000572.3
MANE Select
c.378+284G>A
intron
N/ANP_000563.1
IL10
NM_001382624.1
c.123+284G>A
intron
N/ANP_001369553.1
IL10
NR_168466.1
n.437+284G>A
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IL10
ENST00000423557.1
TSL:1 MANE Select
c.378+284G>A
intron
N/AENSP00000412237.1
IL10
ENST00000659065.2
c.261+284G>A
intron
N/AENSP00000499588.1
IL10
ENST00000659642.2
c.261+284G>A
intron
N/AENSP00000499509.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000623
AC:
2
AN:
320896
Hom.:
0
Cov.:
0
AF XY:
0.0000118
AC XY:
2
AN XY:
169206
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
9664
American (AMR)
AF:
0.0000697
AC:
1
AN:
14354
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
9900
East Asian (EAS)
AF:
0.00
AC:
0
AN:
20978
South Asian (SAS)
AF:
0.00
AC:
0
AN:
37920
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
18284
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1408
European-Non Finnish (NFE)
AF:
0.00000527
AC:
1
AN:
189878
Other (OTH)
AF:
0.00
AC:
0
AN:
18510
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
4549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
14
DANN
Benign
0.75
PhyloP100
0.74
PromoterAI
0.12
Neutral

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

Other links and lift over

dbSNP: rs3024493; hg19: chr1-206943968; API