1-206785242-G-A

Variant names:

• chr1-206785242-G-A
• rs17015865
• NM_153758.5:c.-148-13619G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153758.5(IL19):​c.-148-13619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,070 control chromosomes in the GnomAD database, including 3,399 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 0.20 (3399 hom., cov: 32)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-148-13619G>A		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-148-13619G>A		intron_variant	Intron 1 of 6		NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-148-13619G>A		intron_variant	Intron 1 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-148-13619G>A		intron_variant	Intron 1 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.68-13619G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30929 AN: 151952 Hom.: 3400 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00576

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.203 AC: 30944 AN: 152070 Hom.: 3399 Cov.: 32 AF XY: 0.197 AC XY: 14665 AN XY: 74332

African (AFR) AF: 0.221 AC: 9160 AN: 41456

American (AMR) AF: 0.129 AC: 1978 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3464

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5194

South Asian (SAS) AF: 0.0985 AC: 475 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2221 AN: 10562

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15957 AN: 67982

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.203 Hom.: 1684

Bravo AF: 0.197

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.48
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs17015865; hg19: chr1-206958587;