rs1554286

chr1-206770888-A-Gchr1-206770888-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153758.5(IL19):c.-339A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 1,612,424 control chromosomes in the GnomAD database, including 500,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40862 hom., cov: 30)
  • Exomes 𝑓: 0.79 (459443 hom.)
• Consequence: IL19 NM_153758.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.114

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-206770888-A-G is Benign according to our data. Variant chr1-206770888-A-G is described in ClinVar as [Benign]. Clinvar id is 1166834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-206770888-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL19	NM_153758.5	c.-339A>G		5_prime_UTR_variant	1/7	ENST00000659997.3
IL10	NM_000572.3	c.378+19T>C		intron_variant		ENST00000423557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL19	ENST00000659997.3	c.-339A>G		5_prime_UTR_variant	1/7		NM_153758.5	P1
IL10	ENST00000423557.1	c.378+19T>C		intron_variant		1	NM_000572.3	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109793 AN: 151870 Hom.: 40839 Cov.: 30

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.718

GnomAD3 exomes AF: 0.718 AC: 180270 AN: 251146 Hom.: 67310 AF XY: 0.723 AC XY: 98240 AN XY: 135794

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.823

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.649

Gnomad FIN exome AF: 0.822

Gnomad NFE exome AF: 0.812

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.787 AC: 1148859 AN: 1460436 Hom.: 459443 Cov.: 38 AF XY: 0.784 AC XY: 569439 AN XY: 726620

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.723 AC: 109876 AN: 151988 Hom.: 40862 Cov.: 30 AF XY: 0.720 AC XY: 53453 AN XY: 74290

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.719

Alfa AF: 0.777 Hom.: 26557

Bravo AF: 0.708

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. Only high quality variants are reported. -

Inflammatory bowel disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.6
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs1554286; hg19: chr1-206944233; COSMIC: COSV65594576; COSMIC: COSV65594576;