chr1-206842612-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153758.5(IL19):​c.524T>G​(p.Phe175Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067169845).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	NM_153758.5	MANE Select	c.524T>G	p.Phe175Cys	missense	Exon 7 of 7	NP_715639.2
	IL19	NM_001369605.1		c.524T>G	p.Phe175Cys	missense	Exon 6 of 6	NP_001356534.1
	IL19	NM_001393490.1		c.524T>G	p.Phe175Cys	missense	Exon 7 of 7	NP_001380419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL19	ENST00000659997.3	MANE Select	c.524T>G	p.Phe175Cys	missense	Exon 7 of 7	ENSP00000499459.2
	IL19	ENST00000270218.10	TSL:1	c.524T>G	p.Phe175Cys	missense	Exon 7 of 7	ENSP00000270218.6
	IL19	ENST00000340758.7	TSL:1	c.524T>G	p.Phe175Cys	missense	Exon 6 of 6	ENSP00000343000.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000555 AC: 1 AN: 180250 AF XY: 0.00

Gnomad AFR exome AF: 0.0000899

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1403458 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 694110

African (AFR) AF: 0.00 AC: 0 AN: 32296

American (AMR) AF: 0.00 AC: 0 AN: 37780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25342

East Asian (EAS) AF: 0.00 AC: 0 AN: 37946

South Asian (SAS) AF: 0.00 AC: 0 AN: 80092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075854

Other (OTH) AF: 0.00 AC: 0 AN: 58230

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74234

African (AFR) AF: 0.0000242 AC: 1 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15264

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 198959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.58
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.14
Sift	Benign	0.031	D
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.13		Loss of glycosylation at S176 (P = 0.0488)
MVP		0.23
MPC		0.33
ClinPred		0.13	T
GERP RS		4.7
Varity_R		0.057
gMVP		0.39
Mutation Taster		=100/0	polymorphism

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;