rs2222202

Positions:

• chr1-206772036-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000572.3(IL10):​c.165+235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,132 control chromosomes in the GnomAD database, including 12,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (12268 hom., cov: 33)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.165+235C>T		intron_variant		ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-149+958G>A		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+1206G>A		intron_variant			NP_001380419.1
IL10	NR_168466.1	n.224+235C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.165+235C>T		intron_variant		1	NM_000572.3	ENSP00000412237	P1
IL19	ENST00000659997.3	c.-149+958G>A		intron_variant			NM_153758.5	ENSP00000499459	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58333 AN: 152014 Hom.: 12263 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.384 AC: 58363 AN: 152132 Hom.: 12268 Cov.: 33 AF XY: 0.377 AC XY: 28029 AN XY: 74382

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.362

Alfa AF: 0.440 Hom.: 6987

Bravo AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.64

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: rs2222202; hg19: chr1-206945381;