rs2243176

Positions:

• chr1-206839099-C-T

Variant summary

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

The NM_153758.5(IL19):​c.211-751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,148 control chromosomes in the GnomAD database, including 2,069 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 0.15 (2069 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.89

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL19	NM_153758.5	c.211-751C>T		intron_variant		ENST00000659997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL19	ENST00000659997.3	c.211-751C>T		intron_variant			NM_153758.5	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23468 AN: 152030 Hom.: 2064 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.154 AC: 23489 AN: 152148 Hom.: 2069 Cov.: 32 AF XY: 0.160 AC XY: 11913 AN XY: 74376

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.160

Alfa AF: 0.155 Hom.: 2470

Bravo AF: 0.156

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.37

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: rs2243176; hg19: chr1-207012444;