NM_000572.3:c.165+305T>G

Variant names:

• chr1-206771966-A-C
• rs3024490
• NM_000572.3:c.165+305T>G

Variant summary

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

The NM_000572.3(IL10):​c.165+305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,146 control chromosomes in the GnomAD database, including 36,740 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 0.69 (36740 hom., cov: 33)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 66 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=-0.88).
• 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_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.165+305T>G		intron	N/A	NP_000563.1
	IL19	NM_153758.5	MANE Select	c.-149+888A>C		intron	N/A	NP_715639.2
	IL19	NM_001393490.1		c.-149+1136A>C		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.165+305T>G		intron	N/A	ENSP00000412237.1
	IL19	ENST00000659997.3	MANE Select	c.-149+888A>C		intron	N/A	ENSP00000499459.2
	IL19	ENST00000656872.2		c.-149+1136A>C		intron	N/A	ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104353 AN: 152028 Hom.: 36715 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.686 AC: 104438 AN: 152146 Hom.: 36740 Cov.: 33 AF XY: 0.683 AC XY: 50773 AN XY: 74388

African (AFR) AF: 0.589 AC: 24428 AN: 41472

American (AMR) AF: 0.674 AC: 10313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2601 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1649 AN: 5182

South Asian (SAS) AF: 0.563 AC: 2715 AN: 4826

European-Finnish (FIN) AF: 0.777 AC: 8217 AN: 10582

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52235 AN: 67996

Other (OTH) AF: 0.680 AC: 1434 AN: 2110

Alfa AF: 0.724 Hom.: 19144

Bravo AF: 0.674

Asia WGS AF: 0.489 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.55
PhyloP100		-0.058
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: rs3024490; hg19: chr1-206945311;