rs3024498

Variant names:

• chr1-206768184-T-C
• rs3024498
• NM_000572.3:c.*452A>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.*452A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 241,398 control chromosomes in the GnomAD database, including 5,659 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 0.20 (3448 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2211 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 116 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.*452A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1
IL10	NR_168466.1	n.1286A>G		non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1	n.816A>G		non_coding_transcript_exon_variant	Exon 3 of 3
IL10	NM_001382624.1	c.*452A>G		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.*452A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29781 AN: 151752 Hom.: 3447 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.196 AC: 17578 AN: 89528 Hom.: 2211 Cov.: 0 AF XY: 0.195 AC XY: 8591 AN XY: 44022

African (AFR) AF: 0.126 AC: 414 AN: 3284

American (AMR) AF: 0.147 AC: 609 AN: 4136

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 788 AN: 4462

East Asian (EAS) AF: 0.00366 AC: 40 AN: 10936

South Asian (SAS) AF: 0.113 AC: 394 AN: 3500

European-Finnish (FIN) AF: 0.240 AC: 157 AN: 654

Middle Eastern (MID) AF: 0.122 AC: 57 AN: 468

European-Non Finnish (NFE) AF: 0.248 AC: 13807 AN: 55604

Other (OTH) AF: 0.202 AC: 1312 AN: 6484

GnomAD4 genome AF: 0.196 AC: 29781 AN: 151870 Hom.: 3448 Cov.: 31 AF XY: 0.191 AC XY: 14195 AN XY: 74212

African (AFR) AF: 0.118 AC: 4865 AN: 41376

American (AMR) AF: 0.154 AC: 2356 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3468

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5170

South Asian (SAS) AF: 0.112 AC: 535 AN: 4794

European-Finnish (FIN) AF: 0.244 AC: 2569 AN: 10548

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18139 AN: 67940

Other (OTH) AF: 0.167 AC: 351 AN: 2106

Alfa AF: 0.233 Hom.: 9511

Bravo AF: 0.186

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.52
PhyloP100		-0.67
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: rs3024498; hg19: chr1-206941529;