rs3024493

Positions:

• chr1-206770623-C-A
• chr1-206770623-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000572.3(IL10):​c.378+284G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 472,530 control chromosomes in the GnomAD database, including 4,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1163 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3233 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.737

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-206770623-C-A is Benign according to our data. Variant chr1-206770623-C-A is described in ClinVar as [Benign]. Clinvar id is 1165022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.378+284G>T		intron_variant		ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.123+284G>T		intron_variant			NP_001369553.1
IL10	NR_168466.1	n.437+284G>T		intron_variant
IL10	NR_168467.1	n.-20G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.378+284G>T		intron_variant		1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16592 AN: 152064 Hom.: 1163 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.132 AC: 42284 AN: 320348 Hom.: 3233 Cov.: 0 AF XY: 0.131 AC XY: 22062 AN XY: 168908

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.0665

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.109 AC: 16579 AN: 152182 Hom.: 1163 Cov.: 32 AF XY: 0.108 AC XY: 8004 AN XY: 74392

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.119

Alfa AF: 0.136 Hom.: 1870

Bravo AF: 0.0993

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Inflammatory bowel disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.79

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: rs3024493; hg19: chr1-206943968;