chr1-206769771-T-C

Position:

• chr1-206769771-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.444+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,310,722 control chromosomes in the GnomAD database, including 140 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 0.0052 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (127 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.82).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.444+58A>G		intron_variant		ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.189+58A>G		intron_variant			NP_001369553.1
IL10	NR_168466.1	n.741+58A>G		intron_variant, non_coding_transcript_variant
IL10	NR_168467.1	n.271+58A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.444+58A>G		intron_variant		1	NM_000572.3	ENSP00000412237	P1

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 782 AN: 152124 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00463 AC: 5367 AN: 1158480 Hom.: 127 Cov.: 16 AF XY: 0.00432 AC XY: 2554 AN XY: 591190

Gnomad4 AFR exome AF: 0.000473

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.00326

Gnomad4 EAS exome AF: 0.0559

Gnomad4 SAS exome AF: 0.00199

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.000554

Gnomad4 OTH exome AF: 0.00435

GnomAD4 genome AF: 0.00516 AC: 786 AN: 152242 Hom.: 13 Cov.: 32 AF XY: 0.00646 AC XY: 481 AN XY: 74452

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0250

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0344

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00329 Hom.: 0

Bravo AF: 0.00674

Asia WGS AF: 0.0200 AC: 69 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	0.89
DANN	Benign	0.61

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: rs5743627; hg19: chr1-206943116;