Variant 1-206842612-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F175S) has been classified as Likely benign.

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Variant links:

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]

IL19 links:

LOC105372878 (HGNC:):

LOC105372878 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067169845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5 linkuse as main transcript	c.524T>G	p.Phe175Cys	missense_variant	7/7	ENST00000659997.3	NP_715639.2
LOC105372878	XR_922482.3 linkuse as main transcript	n.210A>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3 linkuse as main transcript	c.524T>G	p.Phe175Cys	missense_variant	7/7		NM_153758.5	ENSP00000499459	P1	Q9UHD0-1
IL19	ENST00000270218.10 linkuse as main transcript	c.524T>G	p.Phe175Cys	missense_variant	7/7	1		ENSP00000270218	P1	Q9UHD0-1
IL19	ENST00000340758.7 linkuse as main transcript	c.524T>G	p.Phe175Cys	missense_variant	6/6	1		ENSP00000343000	P1	Q9UHD0-1
IL19	ENST00000656872.2 linkuse as main transcript	c.524T>G	p.Phe175Cys	missense_variant	7/7			ENSP00000499487	P1	Q9UHD0-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00000555

AC:

AN:

180250

Hom.:

AF XY:

0.00

AC XY:

AN XY:

95042

show subpopulations

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 SAS 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:

AN:

1403458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694110

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.042

.;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.41

T;.;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

0.23

N;N;.

REVEL

Benign

0.14

Sift

Benign

0.031

D;D;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.11

MutPred

0.13

.;Loss of glycosylation at S176 (P = 0.0488);Loss of glycosylation at S176 (P = 0.0488);

MVP

0.23

MPC

0.33

ClinPred

0.13

GERP RS

4.7

Varity_R

0.057

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over