rs9282739

Positions:

• chr1-206768308-AT-A
• chr1-206768308-AT-ATT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000572.3(IL10):​c.*327del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 323,698 control chromosomes in the GnomAD database, including 186 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (166 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (20 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10	NM_000572.3	c.*327del		3_prime_UTR_variant	5/5	ENST00000423557.1
IL10	NM_001382624.1	c.*327del		3_prime_UTR_variant	3/3
IL10	NR_168466.1	n.1161del		non_coding_transcript_exon_variant	6/6
IL10	NR_168467.1	n.691del		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10	ENST00000423557.1	c.*327del		3_prime_UTR_variant	5/5	1	NM_000572.3	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3792 AN: 151904 Hom.: 166 Cov.: 31

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00616

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00330 AC: 566 AN: 171680 Hom.: 20 Cov.: 0 AF XY: 0.00299 AC XY: 261 AN XY: 87390

Gnomad4 AFR exome AF: 0.0789

Gnomad4 AMR exome AF: 0.00517

Gnomad4 ASJ exome AF: 0.000142

Gnomad4 EAS exome AF: 0.000203

Gnomad4 SAS exome AF: 0.000608

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000312

Gnomad4 OTH exome AF: 0.00641

GnomAD4 genome AF: 0.0250 AC: 3803 AN: 152018 Hom.: 166 Cov.: 31 AF XY: 0.0242 AC XY: 1798 AN XY: 74290

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.00616

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000383

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00448 Hom.: 0

Bravo AF: 0.0286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs9282739; hg19: chr1-206941653;