NM_000572.3:c.379-112A>G

Variant names:

• chr1-206770006-T-C
• rs3024494
• NM_000572.3:c.379-112A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000572.3(IL10):​c.379-112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 792,986 control chromosomes in the GnomAD database, including 391,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.98 (72789 hom., cov: 31)
  • Exomes 𝑓: 1.0 (318477 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-206770006-T-C is Benign according to our data. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206770006-T-C is described in CliVar as Benign. Clinvar id is 2628140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.379-112A>G		intron_variant	Intron 3 of 4	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.124-112A>G		intron_variant	Intron 1 of 2		NP_001369553.1
IL10	NR_168466.1	n.675+76A>G		intron_variant	Intron 4 of 5
IL10	NR_168467.1	n.206-112A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.379-112A>G		intron_variant	Intron 3 of 4	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.977 AC: 148704 AN: 152182 Hom.: 72737 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.979

GnomAD4 exome AF: 0.997 AC: 638755 AN: 640686 Hom.: 318477 AF XY: 0.998 AC XY: 343149 AN XY: 343994

African (AFR) AF: 0.920 AC: 16143 AN: 17554

American (AMR) AF: 0.995 AC: 36638 AN: 36832

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 20640 AN: 20640

East Asian (EAS) AF: 1.00 AC: 33854 AN: 33854

South Asian (SAS) AF: 1.00 AC: 65933 AN: 65948

European-Finnish (FIN) AF: 1.00 AC: 48052 AN: 48056

Middle Eastern (MID) AF: 0.995 AC: 3231 AN: 3248

European-Non Finnish (NFE) AF: 1.00 AC: 381240 AN: 381322

Other (OTH) AF: 0.994 AC: 33024 AN: 33232

GnomAD4 genome AF: 0.977 AC: 148815 AN: 152300 Hom.: 72789 Cov.: 31 AF XY: 0.978 AC XY: 72858 AN XY: 74466

African (AFR) AF: 0.922 AC: 38286 AN: 41536

American (AMR) AF: 0.988 AC: 15129 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68025 AN: 68038

Other (OTH) AF: 0.979 AC: 2068 AN: 2112

Alfa AF: 0.989 Hom.: 20948

Bravo AF: 0.974

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-0.13
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: rs3024494; hg19: chr1-206943351;