chr1-206770623-C-A

Variant names:

• chr1-206770623-C-A
• rs3024493
• NM_000572.3:c.378+284G>T

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.378+284G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 472,530 control chromosomes in the GnomAD database, including 4,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1163 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3233 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.737
• Publications: 104 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=-0.77).
• BP6: Variant 1-206770623-C-A is Benign according to our data. Variant chr1-206770623-C-A is described in ClinVar as Benign. ClinVar VariationId is 1165022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 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.378+284G>T		intron	N/A	NP_000563.1
	IL10	NM_001382624.1		c.123+284G>T		intron	N/A	NP_001369553.1
	IL10	NR_168466.1		n.437+284G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.378+284G>T		intron	N/A	ENSP00000412237.1
	IL10	ENST00000659065.2		c.261+284G>T		intron	N/A	ENSP00000499588.1
	IL10	ENST00000659642.2		c.261+284G>T		intron	N/A	ENSP00000499509.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16592 AN: 152064 Hom.: 1163 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.132 AC: 42284 AN: 320348 Hom.: 3233 Cov.: 0 AF XY: 0.131 AC XY: 22062 AN XY: 168908

African (AFR) AF: 0.0342 AC: 330 AN: 9660

American (AMR) AF: 0.0665 AC: 954 AN: 14342

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 1597 AN: 9878

East Asian (EAS) AF: 0.0190 AC: 398 AN: 20968

South Asian (SAS) AF: 0.109 AC: 4108 AN: 37854

European-Finnish (FIN) AF: 0.149 AC: 2722 AN: 18240

Middle Eastern (MID) AF: 0.165 AC: 232 AN: 1406

European-Non Finnish (NFE) AF: 0.156 AC: 29480 AN: 189506

Other (OTH) AF: 0.133 AC: 2463 AN: 18494

GnomAD4 genome AF: 0.109 AC: 16579 AN: 152182 Hom.: 1163 Cov.: 32 AF XY: 0.108 AC XY: 8004 AN XY: 74392

African (AFR) AF: 0.0349 AC: 1448 AN: 41526

American (AMR) AF: 0.0788 AC: 1206 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3472

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5184

South Asian (SAS) AF: 0.109 AC: 527 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10652 AN: 67980

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.136 Hom.: 4549

Bravo AF: 0.0993

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Inflammatory bowel disease Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.74
PromoterAI		-0.027	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: rs3024493; hg19: chr1-206943968;