1-206767486-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.*1150T>C		downstream_gene_variant		ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.*1150T>C		downstream_gene_variant			NP_001369553.1
IL10	NR_168466.1	n.*116T>C		downstream_gene_variant
IL10	NR_168467.1	n.*116T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.*1150T>C		downstream_gene_variant		1	NM_000572.3	ENSP00000412237.1
IL10	ENST00000640756.2	n.*116T>C		downstream_gene_variant		5

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.717

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

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.397

Alfa AF: 0.400 Hom.: 2498

Bravo AF: 0.409

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024500; hg19: chr1-206940831;