rs2243187

Variant names:

• chr1-206841003-G-A
• rs2243187
• NM_153758.5:c.364-1G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-206841003-G-A
• chr1-206841003-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PVS1_Strong BS2

The NM_153758.5(IL19):​c.364-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,670 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: IL19 NM_153758.5 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880
• Publications: 3 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]

LOC105372878 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.14044943 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.2, offset of 3, new splice context is: cctccactttatcacaacAGgaa. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153758.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	NM_153758.5	MANE Select	c.364-1G>A		splice_acceptor intron	N/A	NP_715639.2	Q9UHD0-1
	IL19	NM_001369605.1		c.364-1G>A		splice_acceptor intron	N/A	NP_001356534.1	Q9UHD0-1
	IL19	NM_001393490.1		c.364-1G>A		splice_acceptor intron	N/A	NP_001380419.1	Q9UHD0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	ENST00000659997.3	MANE Select	c.364-1G>A		splice_acceptor intron	N/A	ENSP00000499459.2	Q9UHD0-1
	IL19	ENST00000270218.10	TSL:1	c.364-1G>A		splice_acceptor intron	N/A	ENSP00000270218.6	Q9UHD0-1
	IL19	ENST00000340758.7	TSL:1	c.364-1G>A		splice_acceptor intron	N/A	ENSP00000343000.3	Q9UHD0-1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152192 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000760 AC: 191 AN: 251350 AF XY: 0.000456

Gnomad AFR exome AF: 0.00948

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000297 AC: 434 AN: 1461360 Hom.: 1 Cov.: 30 AF XY: 0.000243 AC XY: 177 AN XY: 727014

African (AFR) AF: 0.00950 AC: 318 AN: 33464

American (AMR) AF: 0.000917 AC: 41 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111570

Other (OTH) AF: 0.000894 AC: 54 AN: 60372

GnomAD4 genome AF: 0.00320 AC: 488 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00290 AC XY: 216 AN XY: 74480

African (AFR) AF: 0.0111 AC: 460 AN: 41558

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00115 Hom.: 2

Bravo AF: 0.00405

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000980 AC: 119

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Benign	0.91
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.65	D
PhyloP100		0.88
GERP RS		2.1
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: 4
DS_AL_spliceai		0.65		Position offset: 1

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

Other links and lift over

dbSNP: rs2243187; hg19: chr1-207014348; COSMIC: COSV54283172; COSMIC: COSV54283172;