1-206770368-G-C

Variant names:

• chr1-206770368-G-C
• rs1878672
• NM_000572.3:c.379-474C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 58 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 -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 rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.379-474C>G		intron_variant	Intron 3 of 4	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.124-474C>G		intron_variant	Intron 1 of 2		NP_001369553.1
IL10	NR_168466.1	n.438-49C>G		intron_variant	Intron 3 of 5
IL10	NR_168467.1	n.205+31C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.379-474C>G		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.267 AC: 1137 AN: 4266

American (AMR) AF: 0.277 AC: 1514 AN: 5460

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1249 AN: 3040

East Asian (EAS) AF: 0.0533 AC: 332 AN: 6224

South Asian (SAS) AF: 0.256 AC: 4906 AN: 19182

European-Finnish (FIN) AF: 0.428 AC: 2177 AN: 5084

Middle Eastern (MID) AF: 0.403 AC: 190 AN: 472

European-Non Finnish (NFE) AF: 0.474 AC: 33445 AN: 70514

Other (OTH) AF: 0.411 AC: 2577 AN: 6276

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

African (AFR) AF: 0.289 AC: 11994 AN: 41470

American (AMR) AF: 0.297 AC: 4540 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3470

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5180

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4816

European-Finnish (FIN) AF: 0.471 AC: 4976 AN: 10564

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33046 AN: 67962

Other (OTH) AF: 0.368 AC: 775 AN: 2108

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
PhyloP100		-2.4
PromoterAI		-0.015	Neutral
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: rs1878672; hg19: chr1-206943713;