rs9282739

Variant names:

• chr1-206768308-AT-A
• rs9282739
• NM_000572.3:c.*327delA

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000572.3(IL10):​c.*327delA 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
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 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.*327delA		3_prime_UTR	Exon 5 of 5	NP_000563.1
	IL10	NR_168466.1		n.1161delA		non_coding_transcript_exon	Exon 6 of 6
	IL10	NR_168467.1		n.691delA		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.*327delA		3_prime_UTR	Exon 5 of 5	ENSP00000412237.1
	IL10	ENST00000367099.4	TSL:4	n.1869delA		non_coding_transcript_exon	Exon 2 of 2
	IL10	ENST00000640756.2	TSL:5	n.674delA		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.0789 AC: 413 AN: 5236

American (AMR) AF: 0.00517 AC: 33 AN: 6378

Ashkenazi Jewish (ASJ) AF: 0.000142 AC: 1 AN: 7046

East Asian (EAS) AF: 0.000203 AC: 3 AN: 14744

South Asian (SAS) AF: 0.000608 AC: 10 AN: 16458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4224

Middle Eastern (MID) AF: 0.00253 AC: 2 AN: 790

European-Non Finnish (NFE) AF: 0.000312 AC: 33 AN: 105736

Other (OTH) AF: 0.00641 AC: 71 AN: 11068

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

African (AFR) AF: 0.0877 AC: 3636 AN: 41440

American (AMR) AF: 0.00616 AC: 94 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.000833 AC: 4 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000383 AC: 26 AN: 67960

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.00448 Hom.: 0

Bravo AF: 0.0286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
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: rs9282739; hg19: chr1-206941653;