rs3021094

Variant names:

• chr1-206771607-T-G
• rs3021094
• NM_000572.3:c.166-192A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000572.3(IL10):​c.166-192A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 152,186 control chromosomes in the GnomAD database, including 1,113 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 0.086 (1113 hom., cov: 32)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 94 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.166-192A>C		intron_variant	Intron 1 of 4	ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-149+529T>G		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+777T>G		intron_variant	Intron 1 of 6		NP_001380419.1
IL10	NR_168466.1	n.225-192A>C		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.166-192A>C		intron_variant	Intron 1 of 4	1	NM_000572.3	ENSP00000412237.1
IL19	ENST00000659997.3	c.-149+529T>G		intron_variant	Intron 1 of 6		NM_153758.5	ENSP00000499459.2

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 13089 AN: 152066 Hom.: 1116 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0964

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

GnomAD4 genome AF: 0.0860 AC: 13092 AN: 152186 Hom.: 1113 Cov.: 32 AF XY: 0.0889 AC XY: 6612 AN XY: 74380

African (AFR) AF: 0.0176 AC: 730 AN: 41544

American (AMR) AF: 0.116 AC: 1780 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2470 AN: 5150

South Asian (SAS) AF: 0.104 AC: 502 AN: 4814

European-Finnish (FIN) AF: 0.0881 AC: 934 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5941 AN: 68002

Other (OTH) AF: 0.0958 AC: 202 AN: 2108

Alfa AF: 0.0924 Hom.: 1599

Bravo AF: 0.0887

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.41
PhyloP100		-1.9
PromoterAI		-0.0044	Neutral
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

Other links and lift over

dbSNP: rs3021094; hg19: chr1-206944952;