1-206769068-C-T

Variant names:

• chr1-206769068-C-T
• rs3024495
• NM_000572.3:c.445-340G>A

Variant summary

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

The NM_000572.3(IL10):​c.445-340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,212 control chromosomes in the GnomAD database, including 1,174 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 0.11 (1174 hom., cov: 32)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 29 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Orphanet
• 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).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	NM_000572.3	MANE Select	c.445-340G>A		intron	N/A	NP_000563.1	P22301
	IL10	NM_001382624.1		c.190-340G>A		intron	N/A	NP_001369553.1	A0A286YEX3
	IL10	NR_168466.1		n.742-340G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.445-340G>A		intron	N/A	ENSP00000412237.1	P22301
	IL10	ENST00000659065.2		c.328-340G>A		intron	N/A	ENSP00000499588.1	A0A590UK12
	IL10	ENST00000659642.2		c.328-340G>A		intron	N/A	ENSP00000499509.1	A0A590UK12

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16610 AN: 152094 Hom.: 1174 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.109 AC: 16598 AN: 152212 Hom.: 1174 Cov.: 32 AF XY: 0.108 AC XY: 8028 AN XY: 74414

African (AFR) AF: 0.0349 AC: 1449 AN: 41554

American (AMR) AF: 0.0787 AC: 1204 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3472

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5180

South Asian (SAS) AF: 0.109 AC: 525 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1765 AN: 10580

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10662 AN: 67992

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.0967 Hom.: 413

Bravo AF: 0.0993

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.62
PhyloP100		-0.069
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: rs3024495; hg19: chr1-206942413;