rs3024506

Positions:

• chr1-206771314-A-G

Variant summary

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

The ENST00000423557.1(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 ENST00000423557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd4 at 383 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10	NM_000572.3	c.225+42T>C		intron_variant		ENST00000423557.1	NP_000563.1
IL19	NM_153758.5	c.-149+236A>G		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+484A>G		intron_variant			NP_001380419.1
IL10	NR_168466.1	n.284+42T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1	c.225+42T>C		intron_variant		1	NM_000572.3	ENSP00000412237	P1
IL19	ENST00000659997.3	c.-149+236A>G		intron_variant			NM_153758.5	ENSP00000499459	P1

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

GnomAD3 exomes AF: 0.00224 AC: 558 AN: 248572 Hom.: 3 AF XY: 0.00232 AC XY: 312 AN XY: 134542

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 SAS exome AF: 0.000131

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

Gnomad4 AFR exome AF: 0.000801

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000939

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00384

Gnomad4 OTH exome AF: 0.00248

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

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00391

Gnomad4 OTH AF: 0.00379

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.76

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: rs3024506; hg19: chr1-206944659;