rs2243191

Variant names:

• chr1-206842612-T-C
• rs2243191
• NM_153758.5:c.524T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-206842612-T-C
• chr1-206842612-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153758.5(IL19):​c.524T>C​(p.Phe175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,552,448 control chromosomes in the GnomAD database, including 450,468 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44717 hom., cov: 31)
  • Exomes 𝑓: 0.76 (405751 hom.)
• Consequence: IL19 NM_153758.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 55 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7131254E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.524T>C	p.Phe175Ser	missense_variant	Exon 7 of 7	ENST00000659997.3	NP_715639.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.524T>C	p.Phe175Ser	missense_variant	Exon 7 of 7		NM_153758.5	ENSP00000499459.2
IL19	ENST00000270218.10	c.524T>C	p.Phe175Ser	missense_variant	Exon 7 of 7	1		ENSP00000270218.6
IL19	ENST00000340758.7	c.524T>C	p.Phe175Ser	missense_variant	Exon 6 of 6	1		ENSP00000343000.3
IL19	ENST00000656872.2	c.524T>C	p.Phe175Ser	missense_variant	Exon 7 of 7			ENSP00000499487.2

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115618 AN: 151942 Hom.: 44669 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.752

GnomAD2 exomes AF: 0.708 AC: 127668 AN: 180250 AF XY: 0.710

Gnomad AFR exome AF: 0.825

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.833

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.736

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.739

GnomAD4 exome AF: 0.756 AC: 1058304 AN: 1400388 Hom.: 405751 Cov.: 27 AF XY: 0.754 AC XY: 522040 AN XY: 692732

African (AFR) AF: 0.831 AC: 26799 AN: 32240

American (AMR) AF: 0.634 AC: 23944 AN: 37744

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 21096 AN: 25320

East Asian (EAS) AF: 0.289 AC: 10937 AN: 37898

South Asian (SAS) AF: 0.684 AC: 54768 AN: 80014

European-Finnish (FIN) AF: 0.733 AC: 36779 AN: 50202

Middle Eastern (MID) AF: 0.724 AC: 4108 AN: 5672

European-Non Finnish (NFE) AF: 0.780 AC: 836610 AN: 1073188

Other (OTH) AF: 0.745 AC: 43263 AN: 58110

GnomAD4 genome AF: 0.761 AC: 115719 AN: 152060 Hom.: 44717 Cov.: 31 AF XY: 0.754 AC XY: 56026 AN XY: 74332

African (AFR) AF: 0.818 AC: 33920 AN: 41470

American (AMR) AF: 0.692 AC: 10570 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2886 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1698 AN: 5152

South Asian (SAS) AF: 0.680 AC: 3270 AN: 4806

European-Finnish (FIN) AF: 0.737 AC: 7797 AN: 10584

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53048 AN: 67986

Other (OTH) AF: 0.752 AC: 1589 AN: 2112

Alfa AF: 0.762 Hom.: 198959

Bravo AF: 0.756

TwinsUK AF: 0.793 AC: 2940

ALSPAC AF: 0.769 AC: 2962

ESP6500AA AF: 0.832 AC: 3663

ESP6500EA AF: 0.778 AC: 6682

ExAC AF: 0.674 AC: 76441

Asia WGS AF: 0.568 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.15
DEOGEN2	Benign	0.032	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.29	T;.;T
MetaRNN	Benign	0.0000017	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.3	.;N;N
PhyloP100		0.15
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.3	N;N;.
REVEL	Benign	0.18
Sift	Benign	1.0	T;T;.
Sift4G	Benign	0.73	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.063
MPC		0.41
ClinPred		0.0028	T
GERP RS		4.7
Varity_R		0.034
gMVP		0.41
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: rs2243191; hg19: chr1-207015957; COSMIC: COSV54282787; COSMIC: COSV54282787;