rs1518110

Variant names:

• chr1-206771516-A-C
• rs1518110
• NM_000572.3:c.166-101T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 59 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 2628131.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.166-101T>G		intron_variant	Intron 1 of 4	ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-149+438A>C		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+686A>C		intron_variant	Intron 1 of 6		NP_001380419.1
IL10	NR_168466.1	n.225-101T>G		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.166-101T>G		intron_variant	Intron 1 of 4	1	NM_000572.3	ENSP00000412237.1
IL19	ENST00000659997.3	c.-149+438A>C		intron_variant	Intron 1 of 6		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

African (AFR) AF: 0.596 AC: 12125 AN: 20330

American (AMR) AF: 0.628 AC: 21352 AN: 33974

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 16711 AN: 21558

East Asian (EAS) AF: 0.336 AC: 11198 AN: 33316

South Asian (SAS) AF: 0.617 AC: 40638 AN: 65880

European-Finnish (FIN) AF: 0.802 AC: 38245 AN: 47666

Middle Eastern (MID) AF: 0.734 AC: 3008 AN: 4100

European-Non Finnish (NFE) AF: 0.790 AC: 437645 AN: 553948

Other (OTH) AF: 0.726 AC: 28134 AN: 38748

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

African (AFR) AF: 0.592 AC: 24475 AN: 41350

American (AMR) AF: 0.681 AC: 10397 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1643 AN: 5164

South Asian (SAS) AF: 0.580 AC: 2788 AN: 4804

European-Finnish (FIN) AF: 0.808 AC: 8496 AN: 10514

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53685 AN: 67910

Other (OTH) AF: 0.687 AC: 1451 AN: 2112

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

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.59
PromoterAI		-0.032	Neutral
Mutation Taster		=20/80	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs1518110; hg19: chr1-206944861;