rs3024509

Variant names:

• chr1-206769952-A-G
• rs3024509
• NM_000572.3:c.379-58T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000423557.1(IL10):​c.379-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,384,938 control chromosomes in the GnomAD database, including 2,411 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 0.043 (178 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2233 hom.)
• Consequence: IL10 ENST00000423557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 47 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423557.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	NM_000572.3	MANE Select	c.379-58T>C		intron	N/A	NP_000563.1
	IL10	NM_001382624.1		c.124-58T>C		intron	N/A	NP_001369553.1
	IL10	NR_168466.1		n.676-58T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.379-58T>C		intron	N/A	ENSP00000412237.1
	IL10	ENST00000659065.2		c.262-58T>C		intron	N/A	ENSP00000499588.1
	IL10	ENST00000659642.2		c.262-58T>C		intron	N/A	ENSP00000499509.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6541 AN: 152194 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.0554 AC: 68251 AN: 1232626 Hom.: 2233 AF XY: 0.0545 AC XY: 34041 AN XY: 624340

African (AFR) AF: 0.0100 AC: 290 AN: 28948

American (AMR) AF: 0.0440 AC: 1939 AN: 44086

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 2101 AN: 24586

East Asian (EAS) AF: 0.000130 AC: 5 AN: 38550

South Asian (SAS) AF: 0.0198 AC: 1609 AN: 81394

European-Finnish (FIN) AF: 0.0592 AC: 3146 AN: 53104

Middle Eastern (MID) AF: 0.0861 AC: 447 AN: 5192

European-Non Finnish (NFE) AF: 0.0616 AC: 55642 AN: 903998

Other (OTH) AF: 0.0582 AC: 3072 AN: 52768

GnomAD4 genome AF: 0.0429 AC: 6541 AN: 152312 Hom.: 178 Cov.: 32 AF XY: 0.0431 AC XY: 3207 AN XY: 74482

African (AFR) AF: 0.0126 AC: 522 AN: 41588

American (AMR) AF: 0.0468 AC: 717 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4826

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4095 AN: 68014

Other (OTH) AF: 0.0527 AC: 111 AN: 2108

Alfa AF: 0.0574 Hom.: 268

Bravo AF: 0.0419

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.86
DANN	Benign	0.58
PhyloP100		-0.55
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: rs3024509; hg19: chr1-206943297;