1-206771701-C-A

Variant names:

• chr1-206771701-C-A
• rs3024491
• NM_000572.3:c.166-286G>T

Variant summary

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

The NM_000572.3(IL10):​c.166-286G>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 152,090 control chromosomes in the GnomAD database, including 12,267 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 (12267 hom., cov: 32)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 55 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	NM_000572.3	MANE Select	c.166-286G>T		intron	N/A	NP_000563.1
	IL19	NM_153758.5	MANE Select	c.-149+623C>A		intron	N/A	NP_715639.2
	IL19	NM_001393490.1		c.-149+871C>A		intron	N/A	NP_001380419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.166-286G>T		intron	N/A	ENSP00000412237.1
	IL19	ENST00000659997.3	MANE Select	c.-149+623C>A		intron	N/A	ENSP00000499459.2
	IL19	ENST00000656872.2		c.-149+871C>A		intron	N/A	ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58319 AN: 151972 Hom.: 12262 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.384 AC: 58349 AN: 152090 Hom.: 12267 Cov.: 32 AF XY: 0.377 AC XY: 28006 AN XY: 74346

African (AFR) AF: 0.290 AC: 12027 AN: 41474

American (AMR) AF: 0.293 AC: 4476 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3470

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5186

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4983 AN: 10564

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32921 AN: 67984

Other (OTH) AF: 0.360 AC: 757 AN: 2104

Alfa AF: 0.325 Hom.: 1441

Bravo AF: 0.368

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.54
PhyloP100		-1.5
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: rs3024491; hg19: chr1-206945046; COSMIC: COSV65594902; COSMIC: COSV65594902;