rs3024506

Variant names:

• chr1-206771314-A-G
• rs3024506
• NM_000572.3:c.225+42T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000572.3(IL10):​c.225+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,561,460 control chromosomes in the GnomAD database, including 6 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 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (5 hom.)
• Consequence: IL10 NM_000572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 0 publications found

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]

IL19 (HGNC:5990): (interleukin 19) The protein encoded by this gene is a cytokine that belongs to the IL10 cytokine subfamily. This cytokine is found to be preferentially expressed in monocytes. It can bind the IL20 receptor complex and lead to the activation of the signal transducer and activator of transcription 3 (STAT3). A similar cytokine in mouse is reported to up-regulate the expression of IL6 and TNF-alpha and induce apoptosis, which suggests a role of this cytokine in inflammatory responses. Alternatively spliced transcript variants encoding the distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAdExome4 at 5 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	NM_000572.3	MANE Select	c.225+42T>C		intron	N/A	NP_000563.1
	IL19	NM_153758.5	MANE Select	c.-149+236A>G		intron	N/A	NP_715639.2
	IL19	NM_001393490.1		c.-149+484A>G		intron	N/A	NP_001380419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10	ENST00000423557.1	TSL:1 MANE Select	c.225+42T>C		intron	N/A	ENSP00000412237.1
	IL19	ENST00000659997.3	MANE Select	c.-149+236A>G		intron	N/A	ENSP00000499459.2
	IL19	ENST00000656872.2		c.-149+484A>G		intron	N/A	ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 383 AN: 152004 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00224 AC: 558 AN: 248572 AF XY: 0.00232

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00312 AC: 4400 AN: 1409338 Hom.: 5 Cov.: 26 AF XY: 0.00303 AC XY: 2132 AN XY: 704226

African (AFR) AF: 0.000801 AC: 26 AN: 32440

American (AMR) AF: 0.00244 AC: 109 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25778

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.0000939 AC: 8 AN: 85200

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53392

Middle Eastern (MID) AF: 0.000198 AC: 1 AN: 5046

European-Non Finnish (NFE) AF: 0.00384 AC: 4088 AN: 1064852

Other (OTH) AF: 0.00248 AC: 145 AN: 58552

GnomAD4 genome AF: 0.00252 AC: 383 AN: 152122 Hom.: 1 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74378

African (AFR) AF: 0.000554 AC: 23 AN: 41490

American (AMR) AF: 0.00379 AC: 58 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00391 AC: 266 AN: 67980

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00291 Hom.: 1

Bravo AF: 0.00269

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		-0.067
PromoterAI		0.25	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3024506; hg19: chr1-206944659;