rs908704

Positions:

• chr1-206826715-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-2-9946G>A		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-2-9946G>A		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-2-9946G>A		intron_variant			NM_153758.5	ENSP00000499459	P1
IL19	ENST00000656872.2	c.-2-9946G>A		intron_variant				ENSP00000499487	P1
IL19	ENST00000662320.1	n.1439G>A		non_coding_transcript_exon_variant	3/3

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

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.727

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs908704; hg19: chr1-207000060; COSMIC: COSV54282885; COSMIC: COSV54282885;