rs3024508

Variant names:

• chr1-206770065-A-C
• rs3024508
• NM_000572.3:c.379-171T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-206770065-A-C
• chr1-206770065-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000572.3(IL10):​c.379-171T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 152,178 control chromosomes in the GnomAD database, including 19 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 0.012 (19 hom., cov: 32)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 7 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0124 (1885/152178) while in subpopulation NFE AF = 0.019 (1290/68010). AF 95% confidence interval is 0.0181. There are 19 homozygotes in GnomAd4. There are 883 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.379-171T>G		intron_variant	Intron 3 of 4	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.124-171T>G		intron_variant	Intron 1 of 2		NP_001369553.1
IL10	NR_168466.1	n.675+17T>G		intron_variant	Intron 4 of 5
IL10	NR_168467.1	n.206-171T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.379-171T>G		intron_variant	Intron 3 of 4	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1885 AN: 152060 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00346

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0124 AC: 1885 AN: 152178 Hom.: 19 Cov.: 32 AF XY: 0.0119 AC XY: 883 AN XY: 74398

African (AFR) AF: 0.00345 AC: 143 AN: 41498

American (AMR) AF: 0.0100 AC: 153 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4820

European-Finnish (FIN) AF: 0.0196 AC: 207 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0190 AC: 1290 AN: 68010

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0160 Hom.: 27

Bravo AF: 0.0111

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.10
DANN	Benign	0.73
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs3024508; hg19: chr1-206943410;