1-206770368-G-C

Position:

• chr1-206770368-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000572.3(IL10):​c.379-474C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 272,564 control chromosomes in the GnomAD database, including 22,862 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 0.39 (12356 hom., cov: 32)
  • Exomes 𝑓: 0.39 (10506 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.379-474C>G		intron_variant		ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.124-474C>G		intron_variant			NP_001369553.1
IL10	NR_168466.1	n.438-49C>G		intron_variant
IL10	NR_168467.1	n.205+31C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.379-474C>G		intron_variant		1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58688 AN: 151928 Hom.: 12352 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.394 AC: 47527 AN: 120518 Hom.: 10506 Cov.: 0 AF XY: 0.379 AC XY: 24146 AN XY: 63784

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.0533

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.386 AC: 58716 AN: 152046 Hom.: 12356 Cov.: 32 AF XY: 0.379 AC XY: 28186 AN XY: 74322

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.368

Alfa AF: 0.311 Hom.: 966

Bravo AF: 0.371

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.019
DANN	Benign	0.36

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: rs1878672; hg19: chr1-206943713;