1-206770888-A-G

Variant names:

• chr1-206770888-A-G
• rs1554286
• NM_153758.5:c.-339A>G

Variant summary

Our verdict is Benign. The variant received -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:3
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-339A>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000659997.3	NP_715639.2
IL10	NM_000572.3	c.378+19T>C		intron_variant	Intron 3 of 4	ENST00000423557.1	NP_000563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997	c.-339A>G		5_prime_UTR_variant	Exon 1 of 7		NM_153758.5	ENSP00000499459.2
IL10	ENST00000423557.1	c.378+19T>C		intron_variant	Intron 3 of 4	1	NM_000572.3	ENSP00000412237.1

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

GnomAD2 exomes AF: 0.718 AC: 180270 AN: 251146 AF XY: 0.723

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 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 AC: 20162 AN: 33436

Gnomad4 AMR exome AF: 0.640 AC: 28607 AN: 44720

Gnomad4 ASJ exome AF: 0.822 AC: 21468 AN: 26132

Gnomad4 EAS exome AF: 0.327 AC: 12962 AN: 39658

Gnomad4 SAS exome AF: 0.657 AC: 56622 AN: 86220

Gnomad4 FIN exome AF: 0.821 AC: 43873 AN: 53412

Gnomad4 NFE exome AF: 0.824 AC: 914733 AN: 1110768

Gnomad4 Remaining exome AF: 0.762 AC: 45976 AN: 60326

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 AC: 0.599029 AN: 0.599029

Gnomad4 AMR AF: 0.707 AC: 0.706856 AN: 0.706856

Gnomad4 ASJ AF: 0.804 AC: 0.80352 AN: 0.80352

Gnomad4 EAS AF: 0.326 AC: 0.326273 AN: 0.326273

Gnomad4 SAS AF: 0.615 AC: 0.615033 AN: 0.615033

Gnomad4 FIN AF: 0.827 AC: 0.82713 AN: 0.82713

Gnomad4 NFE AF: 0.819 AC: 0.81932 AN: 0.81932

Gnomad4 OTH AF: 0.719 AC: 0.719165 AN: 0.719165

Alfa AF: 0.768 Hom.: 35980

Bravo AF: 0.708

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. Only high quality variants are reported. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inflammatory bowel disease Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.43
Mutation Taster		=100/0	polymorphism (auto)

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;