1-206769068-C-T

Variant names:

• chr1-206769068-C-T
• rs3024495
• NM_000572.3:c.445-340G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000572.3(IL10):​c.445-340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,212 control chromosomes in the GnomAD database, including 1,174 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 0.11 (1174 hom., cov: 32)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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=-0.83).
• 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 rank	MANE	Protein	UniProt
IL10	NM_000572.3	c.445-340G>A		intron_variant	Intron 4 of 4	ENST00000423557.1	NP_000563.1
IL10	NM_001382624.1	c.190-340G>A		intron_variant	Intron 2 of 2		NP_001369553.1
IL10	NR_168466.1	n.742-340G>A		intron_variant	Intron 5 of 5
IL10	NR_168467.1	n.272-340G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.445-340G>A		intron_variant	Intron 4 of 4	1	NM_000572.3	ENSP00000412237.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16610 AN: 152094 Hom.: 1174 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16598 AN: 152212 Hom.: 1174 Cov.: 32 AF XY: 0.108 AC XY: 8028 AN XY: 74414

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0903 Hom.: 236

Bravo AF: 0.0993

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.62

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: rs3024495; hg19: chr1-206942413;