rs3024510

Positions:

• chr1-206768291-T-A
• chr1-206768291-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000572.3(IL10):​c.*345A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 317,028 control chromosomes in the GnomAD database, including 2 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 0.0029 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (1 hom.)
• Consequence: IL10 NM_000572.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 448 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.*345A>T		3_prime_UTR_variant	5/5	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.*345A>T		3_prime_UTR_variant	3/3		NP_001369553.1
IL10	NR_168466.1	n.1179A>T		non_coding_transcript_exon_variant	6/6
IL10	NR_168467.1	n.709A>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.*345A>T		3_prime_UTR_variant	5/5	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 448 AN: 151970 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000679

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00286 AC: 471 AN: 164940 Hom.: 1 Cov.: 0 AF XY: 0.00290 AC XY: 243 AN XY: 83836

Gnomad4 AFR exome AF: 0.000198

Gnomad4 AMR exome AF: 0.00274

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00194

Gnomad4 FIN exome AF: 0.00108

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00308

GnomAD4 genome AF: 0.00295 AC: 448 AN: 152088 Hom.: 1 Cov.: 32 AF XY: 0.00268 AC XY: 199 AN XY: 74366

Gnomad4 AFR AF: 0.000677

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00349

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
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: rs3024510; hg19: chr1-206941636;