rs2243168

chr1-206836043-T-Achr1-206836043-T-Cchr1-206836043-T-G

Variant summary

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

The NM_153758.5(IL19):c.-2-618T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,284 control chromosomes in the GnomAD database, including 55,271 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 0.85 (55271 hom., cov: 33)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL19	NM_153758.5	c.-2-618T>A		intron_variant		ENST00000659997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL19	ENST00000659997.3	c.-2-618T>A		intron_variant			NM_153758.5	P1
IL19	ENST00000270218.10	c.-2-618T>A		intron_variant		1		P1
IL19	ENST00000340758.7	c.-2-618T>A		intron_variant		1		P1
IL19	ENST00000656872.2	c.-2-618T>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128800 AN: 152166 Hom.: 55217 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.847 AC: 128911 AN: 152284 Hom.: 55271 Cov.: 33 AF XY: 0.848 AC XY: 63103 AN XY: 74456

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.862

Alfa AF: 0.872 Hom.: 7251

Bravo AF: 0.832

Asia WGS AF: 0.828 AC: 2880 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	0.31
Dann	Benign	0.52

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: rs2243168; hg19: chr1-207009388;