1-206825361-A-T

Variant names:

• chr1-206825361-A-T
• rs2056225
• NM_153758.5:c.-2-11300A>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.-2-11300A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,254 control chromosomes in the GnomAD database, including 59,595 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 0.88 (59595 hom., cov: 34)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-2-11300A>T		intron_variant	Intron 2 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-2-11300A>T		intron_variant	Intron 2 of 6		NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-2-11300A>T		intron_variant	Intron 2 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-2-11300A>T		intron_variant	Intron 2 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.214-129A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134456 AN: 152136 Hom.: 59538 Cov.: 34

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.884 AC: 134569 AN: 152254 Hom.: 59595 Cov.: 34 AF XY: 0.882 AC XY: 65693 AN XY: 74440

African (AFR) AF: 0.850 AC: 35312 AN: 41536

American (AMR) AF: 0.859 AC: 13142 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3172 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4147 AN: 5174

South Asian (SAS) AF: 0.915 AC: 4418 AN: 4828

European-Finnish (FIN) AF: 0.886 AC: 9393 AN: 10598

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61988 AN: 68036

Other (OTH) AF: 0.885 AC: 1871 AN: 2114

Alfa AF: 0.894 Hom.: 7561

Bravo AF: 0.877

Asia WGS AF: 0.837 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.59
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2056225; hg19: chr1-206998706; COSMIC: COSV54282871; COSMIC: COSV54282871;