NM_153758.5:c.-3+10579A>T

Variant names:

• chr1-206809585-A-T
• rs12409577
• NM_153758.5:c.-3+10579A>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+10579A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,044 control chromosomes in the GnomAD database, including 7,659 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 0.31 (7659 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-3+10579A>T		intron_variant	Intron 2 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-3+10579A>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+10579A>T		intron_variant	Intron 2 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-3+10579A>T		intron_variant	Intron 2 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.213+10579A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47137 AN: 151926 Hom.: 7651 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.310 AC: 47181 AN: 152044 Hom.: 7659 Cov.: 32 AF XY: 0.306 AC XY: 22724 AN XY: 74320

African (AFR) AF: 0.377 AC: 15638 AN: 41456

American (AMR) AF: 0.256 AC: 3909 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5162

South Asian (SAS) AF: 0.180 AC: 870 AN: 4822

European-Finnish (FIN) AF: 0.288 AC: 3048 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20074 AN: 67972

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.187 Hom.: 367

Bravo AF: 0.312

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		-0.047
Mutation Taster		=99/1	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: rs12409577; hg19: chr1-206982930;