chr1-206836043-T-A

Variant names:

• chr1-206836043-T-A
• rs2243168
• NM_153758.5:c.-2-618T>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.-2-618T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,284 control chromosomes in the GnomAD database, including 55,271 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 0.85 (55271 hom., cov: 33)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-2-618T>A		intron_variant	Intron 2 of 6	ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-2-618T>A		intron_variant	Intron 2 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000270218.10	c.-2-618T>A		intron_variant	Intron 2 of 6	1		ENSP00000270218.6
IL19	ENST00000340758.7	c.-2-618T>A		intron_variant	Intron 1 of 5	1		ENSP00000343000.3
IL19	ENST00000656872.2	c.-2-618T>A		intron_variant	Intron 2 of 6			ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128800 AN: 152166 Hom.: 55217 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.847 AC: 128911 AN: 152284 Hom.: 55271 Cov.: 33 AF XY: 0.848 AC XY: 63103 AN XY: 74456

African (AFR) AF: 0.706 AC: 29310 AN: 41536

American (AMR) AF: 0.862 AC: 13193 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3186 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4080 AN: 5184

South Asian (SAS) AF: 0.914 AC: 4409 AN: 4826

European-Finnish (FIN) AF: 0.901 AC: 9570 AN: 10626

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62215 AN: 68014

Other (OTH) AF: 0.862 AC: 1823 AN: 2114

Alfa AF: 0.872 Hom.: 7251

Bravo AF: 0.832

Asia WGS AF: 0.828 AC: 2880 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	0.31
DANN	Benign	0.52
PhyloP100		-1.4
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: rs2243168; hg19: chr1-207009388;