rs908704

Variant names:

• chr1-206826715-G-A
• rs908704
• NM_153758.5:c.-2-9946G>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.-2-9946G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,112 control chromosomes in the GnomAD database, including 40,807 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 0.73 (40807 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-2-9946G>A		intron_variant	Intron 2 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-2-9946G>A		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.-2-9946G>A		intron_variant	Intron 2 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000662320.1	n.1439G>A		non_coding_transcript_exon_variant	Exon 3 of 3
IL19	ENST00000656872.2	c.-2-9946G>A		intron_variant	Intron 2 of 6			ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110434 AN: 151994 Hom.: 40760 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.727 AC: 110533 AN: 152112 Hom.: 40807 Cov.: 31 AF XY: 0.720 AC XY: 53508 AN XY: 74360

African (AFR) AF: 0.662 AC: 27444 AN: 41454

American (AMR) AF: 0.673 AC: 10279 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2759 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2216 AN: 5170

South Asian (SAS) AF: 0.678 AC: 3271 AN: 4824

European-Finnish (FIN) AF: 0.731 AC: 7735 AN: 10588

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54339 AN: 68000

Other (OTH) AF: 0.727 AC: 1538 AN: 2116

Alfa AF: 0.759 Hom.: 5514

Bravo AF: 0.714

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.67
PhyloP100		-0.56
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: rs908704; hg19: chr1-207000060; COSMIC: COSV54282885; COSMIC: COSV54282885;