chr1-206769952-A-G

Position:

• chr1-206769952-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000572.3(IL10):​c.379-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,384,938 control chromosomes in the GnomAD database, including 2,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.043 (178 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2233 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-206769952-A-G is Benign according to our data. Variant chr1-206769952-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.379-58T>C		intron_variant		ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.124-58T>C		intron_variant			NP_001369553.1
IL10	NR_168466.1	n.676-58T>C		intron_variant, non_coding_transcript_variant
IL10	NR_168467.1	n.206-58T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.379-58T>C		intron_variant		1	NM_000572.3	ENSP00000412237	P1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6541 AN: 152194 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.0554 AC: 68251 AN: 1232626 Hom.: 2233 AF XY: 0.0545 AC XY: 34041 AN XY: 624340

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0440

Gnomad4 ASJ exome AF: 0.0855

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0616

Gnomad4 OTH exome AF: 0.0582

GnomAD4 genome AF: 0.0429 AC: 6541 AN: 152312 Hom.: 178 Cov.: 32 AF XY: 0.0431 AC XY: 3207 AN XY: 74482

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0568 Hom.: 208

Bravo AF: 0.0419

Asia WGS AF: 0.00866 AC: 30 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	0.86
DANN	Benign	0.58

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: rs3024509; hg19: chr1-206943297;