rs2243188

chr1-206841127-A-Cchr1-206841127-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153758.5(IL19):c.438+49A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,485,528 control chromosomes in the GnomAD database, including 407,337 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 0.69 (37090 hom., cov: 32)
  • Exomes 𝑓: 0.74 (370247 hom.)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL19	NM_153758.5	c.438+49A>C		intron_variant		ENST00000659997.3
LOC105372878	XR_922482.3	n.701T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL19	ENST00000659997.3	c.438+49A>C		intron_variant			NM_153758.5	P1
IL19	ENST00000270218.10	c.438+49A>C		intron_variant		1		P1
IL19	ENST00000340758.7	c.438+49A>C		intron_variant		1		P1
IL19	ENST00000656872.2	c.438+49A>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104911 AN: 152010 Hom.: 37049 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.700

GnomAD3 exomes AF: 0.690 AC: 171225 AN: 248016 Hom.: 60597 AF XY: 0.698 AC XY: 93554 AN XY: 134084

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.605

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.697

Gnomad FIN exome AF: 0.720

Gnomad NFE exome AF: 0.763

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.741 AC: 987459 AN: 1333400 Hom.: 370247 Cov.: 19 AF XY: 0.740 AC XY: 495739 AN XY: 670050

Gnomad4 AFR exome AF: 0.592

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.789

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.693

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.690 AC: 105005 AN: 152128 Hom.: 37090 Cov.: 32 AF XY: 0.685 AC XY: 50946 AN XY: 74356

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.701

Alfa AF: 0.698 Hom.: 6001

Bravo AF: 0.674

Asia WGS AF: 0.562 AC: 1954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.58

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: rs2243188; hg19: chr1-207014472; COSMIC: COSV54282946; COSMIC: COSV54282946;