chr1-206771300-T-C

Variant names:

• chr1-206771300-T-C
• rs1518111
• NM_000572.3:c.225+56A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000572.3(IL10):​c.225+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,471,248 control chromosomes in the GnomAD database, including 423,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38381 hom., cov: 30)
  • Exomes 𝑓: 0.76 (385295 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.399
• Publications: 154 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-206771300-T-C is Benign according to our data. Variant chr1-206771300-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	NM_000572.3	MANE Select	c.225+56A>G		intron	N/A	NP_000563.1	P22301
	IL19	NM_153758.5	MANE Select	c.-149+222T>C		intron	N/A	NP_715639.2	Q9UHD0-1
	IL19	NM_001393490.1		c.-149+470T>C		intron	N/A	NP_001380419.1	Q9UHD0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.225+56A>G		intron	N/A	ENSP00000412237.1	P22301
	IL19	ENST00000659997.3	MANE Select	c.-149+222T>C		intron	N/A	ENSP00000499459.2	Q9UHD0-1
	IL19	ENST00000656872.2		c.-149+470T>C		intron	N/A	ENSP00000499487.2	Q9UHD0-1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106465 AN: 151768 Hom.: 38356 Cov.: 30

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.757 AC: 999032 AN: 1319360 Hom.: 385295 Cov.: 19 AF XY: 0.753 AC XY: 499996 AN XY: 663866

African (AFR) AF: 0.599 AC: 18312 AN: 30568

American (AMR) AF: 0.619 AC: 27519 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 19540 AN: 25208

East Asian (EAS) AF: 0.322 AC: 12541 AN: 38982

South Asian (SAS) AF: 0.618 AC: 51464 AN: 83238

European-Finnish (FIN) AF: 0.802 AC: 42793 AN: 53338

Middle Eastern (MID) AF: 0.731 AC: 3356 AN: 4590

European-Non Finnish (NFE) AF: 0.796 AC: 782595 AN: 983386

Other (OTH) AF: 0.736 AC: 40912 AN: 55596

GnomAD4 genome AF: 0.702 AC: 106550 AN: 151888 Hom.: 38381 Cov.: 30 AF XY: 0.698 AC XY: 51813 AN XY: 74258

African (AFR) AF: 0.593 AC: 24516 AN: 41350

American (AMR) AF: 0.682 AC: 10407 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1626 AN: 5148

South Asian (SAS) AF: 0.581 AC: 2790 AN: 4806

European-Finnish (FIN) AF: 0.809 AC: 8555 AN: 10576

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53733 AN: 67958

Other (OTH) AF: 0.689 AC: 1454 AN: 2110

Alfa AF: 0.745 Hom.: 131736

Bravo AF: 0.686

Asia WGS AF: 0.498 AC: 1736 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inflammatory bowel disease (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		-0.40
PromoterAI		0.12	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: rs1518111; hg19: chr1-206944645; COSMIC: COSV65594326; COSMIC: COSV65594326;