1-206767486-A-G

Variant names:

• chr1-206767486-A-G
• rs3024500
• NM_000572.3:c.*1150T>C

Variant summary

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

The NM_000572.3(IL10):​c.*1150T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,946 control chromosomes in the GnomAD database, including 14,099 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 0.42 (14099 hom., cov: 31)
  • Exomes 𝑓: 0.49 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL10 NM_000572.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 28 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Orphanet
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 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.*1150T>C		downstream_gene	N/A	NP_000563.1	P22301
	IL10	NM_001382624.1		c.*1150T>C		downstream_gene	N/A	NP_001369553.1	A0A286YEX3
	IL10	NR_168466.1		n.*116T>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.*1150T>C		downstream_gene	N/A	ENSP00000412237.1	P22301
	IL10	ENST00000640756.2	TSL:5	n.*116T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63732 AN: 151828 Hom.: 14078 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.395

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.489 AC: 93 AN: 190 Hom.: 24 AF XY: 0.491 AC XY: 56 AN XY: 114

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.397 AC: 54 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.717 AC: 33 AN: 46

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.420 AC: 63801 AN: 151946 Hom.: 14099 Cov.: 31 AF XY: 0.412 AC XY: 30603 AN XY: 74250

African (AFR) AF: 0.406 AC: 16798 AN: 41420

American (AMR) AF: 0.308 AC: 4707 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3466

East Asian (EAS) AF: 0.0520 AC: 269 AN: 5170

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4814

European-Finnish (FIN) AF: 0.472 AC: 4981 AN: 10548

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33072 AN: 67930

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.419 Hom.: 4604

Bravo AF: 0.409

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3024500; hg19: chr1-206940831;