1-206768519-A-G

Variant names:

• chr1-206768519-A-G
• rs3024496
• NM_000572.3:c.*117T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000572.3(IL10):​c.*117T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 695,764 control chromosomes in the GnomAD database, including 64,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14000 hom., cov: 31)
  • Exomes 𝑓: 0.41 (50042 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.453

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-206768519-A-G is Benign according to our data. Variant chr1-206768519-A-G is described in ClinVar as [Benign]. Clinvar id is 2628225.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-206768519-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.*117T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.*117T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001369553.1
IL10	NR_168466.1	n.951T>C		non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1	n.481T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557	c.*117T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63370 AN: 151816 Hom.: 13979 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.408 AC: 221827 AN: 543830 Hom.: 50042 Cov.: 4 AF XY: 0.401 AC XY: 118071 AN XY: 294534

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.418 AC: 63439 AN: 151934 Hom.: 14000 Cov.: 31 AF XY: 0.410 AC XY: 30441 AN XY: 74266

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0311

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.393

Alfa AF: 0.452 Hom.: 17315

Bravo AF: 0.406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.7
DANN	Benign	0.67

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: rs3024496; hg19: chr1-206941864; COSMIC: COSV65594494; COSMIC: COSV65594494;