1-206816263-C-T

Variant names:

• chr1-206816263-C-T
• rs12409415
• NM_153758.5:c.-3+17257C>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.-3+17257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 151,512 control chromosomes in the GnomAD database, including 885 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 0.096 (885 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 12 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-3+17257C>T		intron_variant	Intron 2 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-3+17257C>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.-3+17257C>T		intron_variant	Intron 2 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-3+17257C>T		intron_variant	Intron 2 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.214-9227C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14573 AN: 151394 Hom.: 883 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0930

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

GnomAD4 genome AF: 0.0962 AC: 14581 AN: 151512 Hom.: 885 Cov.: 32 AF XY: 0.0969 AC XY: 7175 AN XY: 74014

African (AFR) AF: 0.154 AC: 6341 AN: 41280

American (AMR) AF: 0.113 AC: 1726 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3470

East Asian (EAS) AF: 0.173 AC: 897 AN: 5176

South Asian (SAS) AF: 0.0585 AC: 280 AN: 4790

European-Finnish (FIN) AF: 0.0726 AC: 753 AN: 10378

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4149 AN: 67868

Other (OTH) AF: 0.0925 AC: 195 AN: 2108

Alfa AF: 0.0729 Hom.: 450

Bravo AF: 0.104

Asia WGS AF: 0.138 AC: 482 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.89
PhyloP100		-0.44
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: rs12409415; hg19: chr1-206989608;