rs3024492

Variant names:

• chr1-206770767-T-A
• rs3024492
• NM_000572.3:c.378+140A>T

Variant summary

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

The NM_000572.3(IL10):​c.378+140A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 863,130 control chromosomes in the GnomAD database, including 21,900 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 0.17 (3076 hom., cov: 32)
  • Exomes 𝑓: 0.21 (18824 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687
• Publications: 33 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]

IL19 (HGNC:5990): (interleukin 19) The protein encoded by this gene is a cytokine that belongs to the IL10 cytokine subfamily. This cytokine is found to be preferentially expressed in monocytes. It can bind the IL20 receptor complex and lead to the activation of the signal transducer and activator of transcription 3 (STAT3). A similar cytokine in mouse is reported to up-regulate the expression of IL6 and TNF-alpha and induce apoptosis, which suggests a role of this cytokine in inflammatory responses. Alternatively spliced transcript variants encoding the distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.378+140A>T		intron_variant	Intron 3 of 4	ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-460T>A		upstream_gene_variant		ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.378+140A>T		intron_variant	Intron 3 of 4	1	NM_000572.3	ENSP00000412237.1
IL19	ENST00000659997.3	c.-460T>A		upstream_gene_variant			NM_153758.5	ENSP00000499459.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26139 AN: 152052 Hom.: 3076 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.213 AC: 151751 AN: 710960 Hom.: 18824 AF XY: 0.209 AC XY: 78648 AN XY: 375544

African (AFR) AF: 0.0429 AC: 828 AN: 19314

American (AMR) AF: 0.147 AC: 5754 AN: 39048

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2862 AN: 19716

East Asian (EAS) AF: 0.00287 AC: 103 AN: 35882

South Asian (SAS) AF: 0.119 AC: 7907 AN: 66250

European-Finnish (FIN) AF: 0.235 AC: 11462 AN: 48762

Middle Eastern (MID) AF: 0.0989 AC: 404 AN: 4084

European-Non Finnish (NFE) AF: 0.261 AC: 115529 AN: 442394

Other (OTH) AF: 0.194 AC: 6902 AN: 35510

GnomAD4 genome AF: 0.172 AC: 26134 AN: 152170 Hom.: 3076 Cov.: 32 AF XY: 0.167 AC XY: 12424 AN XY: 74398

African (AFR) AF: 0.0460 AC: 1912 AN: 41530

American (AMR) AF: 0.136 AC: 2073 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3468

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.243 AC: 2567 AN: 10582

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17992 AN: 67976

Other (OTH) AF: 0.143 AC: 302 AN: 2108

Alfa AF: 0.221 Hom.: 654

Bravo AF: 0.158

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.69
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: rs3024492; hg19: chr1-206944112;