NM_000572.3:c.*117T>C

Variant names:

• chr1-206768519-A-G
• rs3024496
• NM_000572.3:c.*117T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000572.3(IL10):​c.*117T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 695,764 control chromosomes in the GnomAD database, including 64,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14000 hom., cov: 31)
  • Exomes 𝑓: 0.41 (50042 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.453
• Publications: 128 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]

IL10 Gene-Disease associations (from GenCC):

• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-206768519-A-G is Benign according to our data. Variant chr1-206768519-A-G is described in ClinVar as Benign. ClinVar VariationId is 2628225.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.*117T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1
IL10	NR_168466.1	n.951T>C		non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1	n.481T>C		non_coding_transcript_exon_variant	Exon 3 of 3
IL10	NM_001382624.1	c.*117T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001369553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.*117T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63370 AN: 151816 Hom.: 13979 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.408 AC: 221827 AN: 543830 Hom.: 50042 Cov.: 4 AF XY: 0.401 AC XY: 118071 AN XY: 294534

African (AFR) AF: 0.409 AC: 6114 AN: 14944

American (AMR) AF: 0.279 AC: 9035 AN: 32440

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 8276 AN: 19484

East Asian (EAS) AF: 0.0229 AC: 736 AN: 32142

South Asian (SAS) AF: 0.272 AC: 16516 AN: 60810

European-Finnish (FIN) AF: 0.455 AC: 18625 AN: 40902

Middle Eastern (MID) AF: 0.394 AC: 962 AN: 2444

European-Non Finnish (NFE) AF: 0.480 AC: 149139 AN: 310890

Other (OTH) AF: 0.417 AC: 12424 AN: 29774

GnomAD4 genome AF: 0.418 AC: 63439 AN: 151934 Hom.: 14000 Cov.: 31 AF XY: 0.410 AC XY: 30441 AN XY: 74266

African (AFR) AF: 0.405 AC: 16778 AN: 41430

American (AMR) AF: 0.305 AC: 4660 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1407 AN: 3468

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1174 AN: 4828

European-Finnish (FIN) AF: 0.473 AC: 4979 AN: 10536

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32948 AN: 67896

Other (OTH) AF: 0.393 AC: 829 AN: 2112

Alfa AF: 0.452 Hom.: 25215

Bravo AF: 0.406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.7
DANN	Benign	0.67
PhyloP100		0.45
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: rs3024496; hg19: chr1-206941864; COSMIC: COSV65594494; COSMIC: COSV65594494;