1-206768291-T-C

Variant names:

• chr1-206768291-T-C
• rs3024510
• NM_000572.3:c.*345A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000572.3(IL10):​c.*345A>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 0.0000121 in 164,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.*345A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1
IL10	NR_168466.1	n.1179A>G		non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1	n.709A>G		non_coding_transcript_exon_variant	Exon 3 of 3
IL10	NM_001382624.1	c.*345A>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.*345A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000121 AC: 2 AN: 164948 Hom.: 0 Cov.: 0 AF XY: 0.0000239 AC XY: 2 AN XY: 83840

African (AFR) AF: 0.00 AC: 0 AN: 5050

American (AMR) AF: 0.00 AC: 0 AN: 6214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6858

East Asian (EAS) AF: 0.00 AC: 0 AN: 14466

South Asian (SAS) AF: 0.00 AC: 0 AN: 15492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 756

European-Non Finnish (NFE) AF: 0.0000197 AC: 2 AN: 101686

Other (OTH) AF: 0.00 AC: 0 AN: 10728

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		-0.044

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: rs3024510; hg19: chr1-206941636;