rs1518111

chr1-206771300-T-C

Variant summary

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

The NM_000572.3(IL10):c.225+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,471,248 control chromosomes in the GnomAD database, including 423,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38381 hom., cov: 30)
  • Exomes 𝑓: 0.76 (385295 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-206771300-T-C is Benign according to our data. Variant chr1-206771300-T-C is described in ClinVar as [Benign]. Clinvar id is 1166835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-206771300-T-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	UniProt
IL10	NM_000572.3	c.225+56A>G		intron_variant		ENST00000423557.1
IL19	NM_153758.5	c.-149+222T>C		intron_variant		ENST00000659997.3
IL19	NM_001393490.1	c.-149+470T>C		intron_variant
IL10	NR_168466.1	n.284+56A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10	ENST00000423557.1	c.225+56A>G		intron_variant		1	NM_000572.3	P1
IL19	ENST00000659997.3	c.-149+222T>C		intron_variant			NM_153758.5	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106465 AN: 151768 Hom.: 38356 Cov.: 30

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.757 AC: 999032 AN: 1319360 Hom.: 385295 Cov.: 19 AF XY: 0.753 AC XY: 499996 AN XY: 663866

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.702 AC: 106550 AN: 151888 Hom.: 38381 Cov.: 30 AF XY: 0.698 AC XY: 51813 AN XY: 74258

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.689

Alfa AF: 0.751 Hom.: 52441

Bravo AF: 0.686

Asia WGS AF: 0.498 AC: 1736 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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

Inflammatory bowel disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.77

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: rs1518111; hg19: chr1-206944645; COSMIC: COSV65594326; COSMIC: COSV65594326;