1-206773321-C-T

Variant names:

• chr1-206773321-C-T
• rs1800894
• NM_153758.5:c.-149+2243C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 32 publications found

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]

IL10 Gene-Disease associations (from GenCC):

• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+2243C>T		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+2491C>T		intron_variant	Intron 1 of 6		NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+2243C>T		intron_variant	Intron 1 of 6		NM_153758.5	ENSP00000499459.2

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3529 AN: 152186 Hom.: 60 Cov.: 32

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

African (AFR) AF: 0.00724 AC: 301 AN: 41568

American (AMR) AF: 0.0270 AC: 413 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4824

European-Finnish (FIN) AF: 0.0235 AC: 250 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2333 AN: 68022

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0297 Hom.: 166

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
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800894; hg19: chr1-206946666;