rs4072227

Variant names:

• chr1-206784213-C-T
• rs4072227
• NM_153758.5:c.-149+13135C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153758.5(IL19):​c.-149+13135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,212 control chromosomes in the GnomAD database, including 60,521 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 0.89 (60521 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+13135C>T		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+13383C>T		intron_variant	Intron 1 of 6		NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+13135C>T		intron_variant	Intron 1 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-149+13383C>T		intron_variant	Intron 1 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.67+13383C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135343 AN: 152094 Hom.: 60494 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.890 AC: 135427 AN: 152212 Hom.: 60521 Cov.: 31 AF XY: 0.889 AC XY: 66154 AN XY: 74400

African (AFR) AF: 0.833 AC: 34576 AN: 41512

American (AMR) AF: 0.859 AC: 13146 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3322 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3820 AN: 5174

South Asian (SAS) AF: 0.903 AC: 4344 AN: 4812

European-Finnish (FIN) AF: 0.915 AC: 9696 AN: 10598

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63452 AN: 68022

Other (OTH) AF: 0.897 AC: 1899 AN: 2116

Alfa AF: 0.918 Hom.: 117334

Bravo AF: 0.882

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4072227; hg19: chr1-206957558;