1-206773552-T-C

Variant names:

• chr1-206773552-T-C
• rs1800896
• NM_153758.5:c.-149+2474T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PP5_Moderate BP4 BA1

The NM_153758.5(IL19):​c.-149+2474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,018 control chromosomes in the GnomAD database, including 12,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: 𝑓 0.40 (12917 hom., cov: 29)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1 O:1
• Conservation: PhyloP100: 0.0260
• Publications: 1915 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: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP5: Variant 1-206773552-T-C is Pathogenic according to our data. Variant chr1-206773552-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1710531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 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+2474T>C		intron	N/A	NP_715639.2
	IL19	NM_001393490.1		c.-149+2722T>C		intron	N/A	NP_001380419.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	ENST00000659997.3	MANE Select	c.-149+2474T>C		intron	N/A	ENSP00000499459.2
	IL19	ENST00000656872.2		c.-149+2722T>C		intron	N/A	ENSP00000499487.2
	IL10	ENST00000659065.2		c.-15+128A>G		intron	N/A	ENSP00000499588.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60462 AN: 150900 Hom.: 12903 Cov.: 29

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.401 AC: 60505 AN: 151018 Hom.: 12917 Cov.: 29 AF XY: 0.393 AC XY: 28989 AN XY: 73686

African (AFR) AF: 0.337 AC: 13869 AN: 41096

American (AMR) AF: 0.302 AC: 4587 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1414 AN: 3462

East Asian (EAS) AF: 0.0528 AC: 270 AN: 5114

South Asian (SAS) AF: 0.249 AC: 1189 AN: 4772

European-Finnish (FIN) AF: 0.475 AC: 4889 AN: 10300

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 32993 AN: 67808

Other (OTH) AF: 0.378 AC: 792 AN: 2098

Alfa AF: 0.447 Hom.: 68892

Bravo AF: 0.387

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Hepatitis C virus, susceptibility to (1)
-	1	-	Leprosy, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.80
PhyloP100		0.026

Splicing

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

Other links and lift over

dbSNP: rs1800896; hg19: chr1-206946897;