rs1518110

Positions:

• chr1-206771516-A-C
• chr1-206771516-A-G
• chr1-206771516-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000572.3(IL10):​c.166-101T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 971,306 control chromosomes in the GnomAD database, including 270,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (38315 hom., cov: 30)
  • Exomes 𝑓: 0.74 (232391 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.590

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]

IL19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-206771516-A-C is Benign according to our data. Variant chr1-206771516-A-C is described in ClinVar as [Benign]. Clinvar id is 2628131.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206771516-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.166-101T>G		intron_variant		ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-149+438A>C		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+686A>C		intron_variant			NP_001380419.1
IL10	NR_168466.1	n.225-101T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.166-101T>G		intron_variant		1	NM_000572.3	ENSP00000412237.1
IL19	ENST00000659997.3	c.-149+438A>C		intron_variant			NM_153758.5	ENSP00000499459.2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106316 AN: 151668 Hom.: 38290 Cov.: 30

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.743 AC: 609056 AN: 819520 Hom.: 232391 AF XY: 0.739 AC XY: 314185 AN XY: 425170

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.701 AC: 106401 AN: 151786 Hom.: 38315 Cov.: 30 AF XY: 0.697 AC XY: 51698 AN XY: 74162

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.687

Alfa AF: 0.735 Hom.: 5353

Bravo AF: 0.686

Asia WGS AF: 0.498 AC: 1737 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.38

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: rs1518110; hg19: chr1-206944861;