rs3024498

Positions:

• chr1-206768184-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000572.3(IL10):​c.*452A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 241,398 control chromosomes in the GnomAD database, including 5,659 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 0.20 (3448 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2211 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL10	NM_000572.3	c.*452A>G		3_prime_UTR_variant	5/5	ENST00000423557.1
IL10	NM_001382624.1	c.*452A>G		3_prime_UTR_variant	3/3
IL10	NR_168466.1	n.1286A>G		non_coding_transcript_exon_variant	6/6
IL10	NR_168467.1	n.816A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10	ENST00000423557.1	c.*452A>G		3_prime_UTR_variant	5/5	1	NM_000572.3	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29781 AN: 151752 Hom.: 3447 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.196 AC: 17578 AN: 89528 Hom.: 2211 Cov.: 0 AF XY: 0.195 AC XY: 8591 AN XY: 44022

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.00366

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.196 AC: 29781 AN: 151870 Hom.: 3448 Cov.: 31 AF XY: 0.191 AC XY: 14195 AN XY: 74212

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00445

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.167

Alfa AF: 0.237 Hom.: 6523

Bravo AF: 0.186

Asia WGS AF: 0.0640 AC: 222 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	0.54
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024498; hg19: chr1-206941529;