rs2243193

Positions:

• chr1-206842880-A-G
• chr1-206842880-A-T

Variant summary

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

The NM_153758.5(IL19):​c.*258A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 383,218 control chromosomes in the GnomAD database, including 94,916 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 0.68 (36574 hom., cov: 33)
  • Exomes 𝑓: 0.70 (58342 hom.)
• Consequence: IL19 NM_153758.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.*258A>G		3_prime_UTR_variant	7/7	ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.*258A>G		3_prime_UTR_variant	7/7		NM_153758.5	ENSP00000499459	P1
IL19	ENST00000340758.7	c.*258A>G		3_prime_UTR_variant	6/6	1		ENSP00000343000	P1
IL19	ENST00000656872.2	c.*258A>G		3_prime_UTR_variant	7/7			ENSP00000499487	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103969 AN: 152056 Hom.: 36548 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.696 AC: 160883 AN: 231044 Hom.: 58342 Cov.: 0 AF XY: 0.693 AC XY: 82537 AN XY: 119114

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.792

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.708

GnomAD4 genome AF: 0.684 AC: 104043 AN: 152174 Hom.: 36574 Cov.: 33 AF XY: 0.679 AC XY: 50531 AN XY: 74398

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.691

Alfa AF: 0.743 Hom.: 56063

Bravo AF: 0.668

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.6
DANN	Benign	0.82

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: rs2243193; hg19: chr1-207016225; COSMIC: COSV54282970; COSMIC: COSV54282970;