rs1800896

Positions:

• chr1-206773552-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153758.5(IL19):​c.-149+2474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,018 control chromosomes in the GnomAD database, including 12,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency: Genomes: 𝑓 0.40 (12917 hom., cov: 29)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0260

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+2474T>C		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+2722T>C		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+2474T>C		intron_variant			NM_153758.5	ENSP00000499459	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60462 AN: 150900 Hom.: 12903 Cov.: 29

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60505 AN: 151018 Hom.: 12917 Cov.: 29 AF XY: 0.393 AC XY: 28989 AN XY: 73686

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.0528

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.378

Alfa AF: 0.453 Hom.: 32372

Bravo AF: 0.387

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800896; hg19: chr1-206946897;