NM_153758.5:c.364-1G>T

Variant names:

• chr1-206841003-G-T
• rs2243187
• NM_153758.5:c.364-1G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_153758.5(IL19):​c.364-1G>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL19 NM_153758.5 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

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]

LOC105372878 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.14044943 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.9, offset of 3, new splice context is: cctccactttatcacatcAGgaa. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.364-1G>T		splice_acceptor_variant, intron_variant	Intron 5 of 6	ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.364-1G>T		splice_acceptor_variant, intron_variant	Intron 5 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000270218.10	c.364-1G>T		splice_acceptor_variant, intron_variant	Intron 5 of 6	1		ENSP00000270218.6
IL19	ENST00000340758.7	c.364-1G>T		splice_acceptor_variant, intron_variant	Intron 4 of 5	1		ENSP00000343000.3
IL19	ENST00000656872.2	c.364-1G>T		splice_acceptor_variant, intron_variant	Intron 5 of 6			ENSP00000499487.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Benign	0.91
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.69	D
GERP RS		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.65		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2243187; hg19: chr1-207014348;