rs1800871

Variant names:

• chr1-206773289-A-G
• rs1800871
• NM_153758.5:c.-149+2211A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-206773289-A-G
• chr1-206773289-A-C
• chr1-206773289-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153758.5(IL19):​c.-149+2211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,064 control chromosomes in the GnomAD database, including 36,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (36734 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.292
• Publications: 1295 publications found

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]

IL10 Gene-Disease associations (from GenCC):

• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-206773289-A-G is Benign according to our data. Variant chr1-206773289-A-G is described in ClinVar as Benign. ClinVar VariationId is 1166836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153758.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	NM_153758.5	MANE Select	c.-149+2211A>G		intron	N/A	NP_715639.2	Q9UHD0-1
	IL19	NM_001393490.1		c.-149+2459A>G		intron	N/A	NP_001380419.1	Q9UHD0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	ENST00000659997.3	MANE Select	c.-149+2211A>G		intron	N/A	ENSP00000499459.2	Q9UHD0-1
	IL10	ENST00000659642.2		c.-971T>C		5_prime_UTR	Exon 2 of 6	ENSP00000499509.1	A0A590UK12
	IL19	ENST00000656872.2		c.-149+2459A>G		intron	N/A	ENSP00000499487.2	Q9UHD0-1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104313 AN: 151946 Hom.: 36709 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.687 AC: 104398 AN: 152064 Hom.: 36734 Cov.: 31 AF XY: 0.683 AC XY: 50744 AN XY: 74324

African (AFR) AF: 0.589 AC: 24419 AN: 41440

American (AMR) AF: 0.674 AC: 10296 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2601 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1631 AN: 5172

South Asian (SAS) AF: 0.564 AC: 2711 AN: 4810

European-Finnish (FIN) AF: 0.776 AC: 8211 AN: 10580

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.768 AC: 52250 AN: 68004

Other (OTH) AF: 0.681 AC: 1435 AN: 2108

Alfa AF: 0.730 Hom.: 176707

Bravo AF: 0.674

Asia WGS AF: 0.488 AC: 1703 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inflammatory bowel disease (1)
-	1	-	Leprosy, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800871; hg19: chr1-206946634;