chr1-206839099-C-T

Variant names:

• chr1-206839099-C-T
• rs2243176
• NM_153758.5:c.211-751C>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.211-751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,148 control chromosomes in the GnomAD database, including 2,069 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 0.15 (2069 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.89
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.211-751C>T		intron_variant	Intron 4 of 6	ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.211-751C>T		intron_variant	Intron 4 of 6		NM_153758.5	ENSP00000499459.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23468 AN: 152030 Hom.: 2064 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.154 AC: 23489 AN: 152148 Hom.: 2069 Cov.: 32 AF XY: 0.160 AC XY: 11913 AN XY: 74376

African (AFR) AF: 0.110 AC: 4564 AN: 41508

American (AMR) AF: 0.199 AC: 3044 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3466

East Asian (EAS) AF: 0.387 AC: 1999 AN: 5166

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9832 AN: 68000

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.154 Hom.: 3049

Bravo AF: 0.156

Asia WGS AF: 0.268 AC: 934 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	1.6
DANN	Benign	0.37
PhyloP100		-3.9
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: rs2243176; hg19: chr1-207012444;