rs2243191

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (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/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.524T>C	p.Phe175Ser	missense_variant	7/7	ENST00000659997.3	NP_715639.2
LOC105372878	XR_922482.3	n.210A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.524T>C	p.Phe175Ser	missense_variant	7/7		NM_153758.5	ENSP00000499459	P1
IL19	ENST00000270218.10	c.524T>C	p.Phe175Ser	missense_variant	7/7	1		ENSP00000270218	P1
IL19	ENST00000340758.7	c.524T>C	p.Phe175Ser	missense_variant	6/6	1		ENSP00000343000	P1
IL19	ENST00000656872.2	c.524T>C	p.Phe175Ser	missense_variant	7/7			ENSP00000499487	P1

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

GnomAD3 exomes AF: 0.708 AC: 127668 AN: 180250 Hom.: 46770 AF XY: 0.710 AC XY: 67442 AN XY: 95042

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 SAS exome AF: 0.685

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

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.745

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

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.752

Alfa AF: 0.762 Hom.: 95858

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
MutationTaster	Benign	1.0	P;P
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

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: rs2243191; hg19: chr1-207015957; COSMIC: COSV54282787; COSMIC: COSV54282787;