rs2138992

Positions:

• chr1-206821059-A-C

Variant summary

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

The NM_153758.5(IL19):​c.-2-15602A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,086 control chromosomes in the GnomAD database, including 41,098 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 0.73 (41098 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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]

IL19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-2-15602A>C		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-2-15602A>C		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-2-15602A>C		intron_variant			NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-2-15602A>C		intron_variant				ENSP00000499487.2
IL19	ENST00000662320.1	n.214-4431A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110793 AN: 151968 Hom.: 41052 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.729 AC: 110891 AN: 152086 Hom.: 41098 Cov.: 32 AF XY: 0.723 AC XY: 53784 AN XY: 74354

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.728

Alfa AF: 0.770 Hom.: 22719

Bravo AF: 0.714

Asia WGS AF: 0.576 AC: 2001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.68

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: rs2138992; hg19: chr1-206994404; COSMIC: COSV61592535;