rs1554286

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.114

Variant links:

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]

IL19 links:

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]

IL10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
IL19	NM_153758.5 linkuse as main transcript	c.-339A>G		5_prime_UTR_variant	1/7	ENST00000659997.3	NP_715639.2
IL10	NM_000572.3 linkuse as main transcript	c.378+19T>C		intron_variant		ENST00000423557.1	NP_000563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3 linkuse as main transcript	c.-339A>G		5_prime_UTR_variant	1/7		NM_153758.5	ENSP00000499459	P1	Q9UHD0-1
IL10	ENST00000423557.1 linkuse as main transcript	c.378+19T>C		intron_variant		1	NM_000572.3	ENSP00000412237	P1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109793

AN:

151870

Hom.:

40839

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.784

AC XY:

569439

AN XY:

726620

show subpopulations

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.:

AF XY:

0.720

AC XY:

53453

AN XY:

74290

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Inflammatory bowel disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over