rs1800894

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_153758.5(IL19):​c.-149+2243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 152,304 control chromosomes in the GnomAD database, including 60 homozygotes. 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: 𝑓 0.023 ( 60 hom., cov: 32)

Consequence

IL19
NM_153758.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33
Variant links:
Genes affected
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0232 (3533/152304) while in subpopulation NFE AF= 0.0343 (2333/68022). AF 95% confidence interval is 0.0331. There are 60 homozygotes in gnomad4. There are 1665 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL19NM_153758.5 linkuse as main transcriptc.-149+2243C>T intron_variant ENST00000659997.3
IL19NM_001393490.1 linkuse as main transcriptc.-149+2491C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL19ENST00000659997.3 linkuse as main transcriptc.-149+2243C>T intron_variant NM_153758.5 P1Q9UHD0-1

Frequencies

GnomAD3 genomes
AF:
0.0232
AC:
3529
AN:
152186
Hom.:
60
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00724
Gnomad AMI
AF:
0.0406
Gnomad AMR
AF:
0.0270
Gnomad ASJ
AF:
0.0300
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00414
Gnomad FIN
AF:
0.0235
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0343
Gnomad OTH
AF:
0.0301
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0232
AC:
3533
AN:
152304
Hom.:
60
Cov.:
32
AF XY:
0.0224
AC XY:
1665
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00724
Gnomad4 AMR
AF:
0.0270
Gnomad4 ASJ
AF:
0.0300
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00435
Gnomad4 FIN
AF:
0.0235
Gnomad4 NFE
AF:
0.0343
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.0308
Hom.:
56
Bravo
AF:
0.0237
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.14
DANN
Benign
0.61

Splicing

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: rs1800894; hg19: chr1-206946666; API