VCV000226027.4 - ClinVar

NC_000019.10:g.39252525T>G

Germline

Top reviewed classifications are shown here.

Submission summary:

3 submissions

2 submitters

3 conditions

Reviewed by expert panel

Drug response

Mar 2021 by PharmGKB

for interferons, peginterferon alfa-2a, peginterferon alfa-2b and ribavirin response - Efficacy

Drug response

Mar 2021 by PharmGKB

for peginterferon alfa-2a, peginterferon alfa-2b, ribavirin and telaprevir response - Efficacy

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000019.10:g.39252525T>G

Variation ID: 226027 Accession: VCV000226027.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.2 19: 39252525 (GRCh38) [ NCBI UCSC ] 19: 39743165 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 26, 2019	Dec 12, 2021	Mar 29, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000019.10:g.39252525T>G
NC_000019.9:g.39743165T>G
NG_055295.1:g.1332A>C

Protein change

Other names

Canonical SPDI

NC_000019.10:39252524:T:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.13119 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.13119

1000 Genomes Project 30x 0.13523

The Genome Aggregation Database (gnomAD) 0.15536

Trans-Omics for Precision Medicine (TOPMed) 0.16468

Links

dbSNP: rs8099917 PharmGKB Clinical Annotation: 1183888959 PharmGKB Clinical Annotation: 981239773 ClinGen: CA10576189 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
IFNL3		-	-	GRCh38 GRCh38 GRCh37	29	40

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy	drug response (1)	reviewed by expert panel	Mar 24, 2021	RCV000211316.5
interferons, peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy	drug response (1)	reviewed by expert panel	Mar 29, 2021	RCV000211192.4
not provided	Benign (1)	criteria provided, single submitter	Mar 14, 2018	RCV000835188.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
drug response Drug-variant association: Efficacy (Mar 29, 2021)	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine) Method: curation	interferons, peginterferon alfa-2a, peginterferon alfa-2b and ribavirin response - Efficacy Drug used for Hepatitis C, Chronic Affected status: yes Allele origin: germline	PharmGKB Accession: SCV000268411.4 First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021 Comment: Drug is not necessarily used to treat response condition	Publications: PubMed (45) PubMed: 19749757‚ 19749758‚ 20060832‚ 20434452‚ 21048934‚ 21068134‚ 21112657‚ 21112660‚ 21145807‚ 21254157‚ 21321200‚ 21346780‚ 21360545‚ 21374656‚ 21384511‚ 21390311‚ 21466653‚ 21503910‚ 21739446‚ 21745312‚ 21907615‚ 21911885‚ 21931540‚ 21987611‚ 22301466‚ 22328925‚ 22345656‚ 22438096‚ 22863269‚ 23133602‚ 23142377‚ 23281610‚ 23730840‚ 24102823‚ 24308755‚ 24355007‚ 24768758‚ 24929144‚ 25278709‚ 25852275‚ 26003758‚ 26075078‚ 26334898‚ 26699619‚ 26825765 Other databases https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166155435 https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/981239773 Comment: PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing … (more) PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications. (less)
drug response Drug-variant association: Efficacy (Mar 24, 2021)	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine) Method: curation	peginterferon alfa-2a, peginterferon alfa-2b, ribavirin and telaprevir response - Efficacy Drug used for Hepatitis C, Chronic Affected status: yes Allele origin: germline	PharmGKB Accession: SCV000268412.4 First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021 Comment: Drug is not necessarily used to treat response condition	Publications: PubMed (6) PubMed: 20648473‚ 21246582‚ 21628662‚ 24117654‚ 24362944‚ 25393304 Other databases https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166155435 https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/1183888959 Comment: PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in … (more) PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. (less)
Benign (Mar 14, 2018)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000976971.1 First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)

Comment:

PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications.

Comment:

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Peginterferon Therapy in Children With Chronic Hepatitis C: A Nationwide, Multicenter Study in Japan, 2004-2013.	Suzuki M	Journal of pediatric gastroenterology and nutrition	2016	PMID: 26825765
Performance and Value of IFN-Lambda3 and IFN-Lambda4 Genotyping in Patients with Chronic Hepatitis C (CHC) Genotype 2/3 in a Real World Setting.	Wiegand SB	PloS one	2015	PMID: 26699619
Combined Effects of 2 Interleukin 28B Polymorphisms on the Therapeutic Outcome of Hepatitis C Patients With Circulating Cryoglobulins.	Bellanti F	Medicine	2015	PMID: 26334898
MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection.	Asada A	Biomedical reports	2015	PMID: 26075078
Assessment of interleukin 28B genotype as a predictor of response to combined therapy with pegylated interferon plus ribavirin in HCV infected Egyptian patients.	Fathy MM	Cytokine	2015	PMID: 26003758
Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C.	Ishiguro H	World journal of gastroenterology	2015	PMID: 25852275
Predictive value of interferon-lambda gene polymorphisms for treatment response in chronic hepatitis C.	Susser S	PloS one	2014	PMID: 25393304
IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients.	Rosso C	World journal of gastroenterology	2014	PMID: 25278709
KIR3DL1-HLA-Bw4 combination and IL28B polymorphism predict response to Peg-IFN and ribavirin with and without telaprevir in chronic hepatitis C.	Umemura T	Human immunology	2014	PMID: 24929144
IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection.	Eslam M	Journal of hepatology	2014	PMID: 24768758
Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C.	Fujino H	Journal of gastroenterology	2014	PMID: 24362944
Genetic polymorphism in IFNL4 and response to pegylated interferon-α and ribavirin in Japanese chronic hepatitis C patients.	Nozawa Y	Tissue antigens	2014	PMID: 24355007
The novel ss469415590 variant predicts virological response to therapy in patients with chronic hepatitis C virus type 1 infection.	Covolo L	Alimentary pharmacology & therapeutics	2014	PMID: 24308755
Impact of IL28B polymorphisms on 24-week telaprevir-based combination therapy for Asian chronic hepatitis C patients with hepatitis C virus genotype 1b.	Tsubota A	Journal of gastroenterology and hepatology	2014	PMID: 24117654
Strong prediction of virological response to combination therapy by IL28B gene variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4.	Ragheb MM	Liver international : official journal of the International Association for the Study of the Liver	2014	PMID: 24102823
Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection.	Seto WK	Journal of viral hepatitis	2013	PMID: 23730840
Effects of IL-28B gene polymorphism on response to peginterferon plus ribavirin combination therapy for genotype 2 chronic hepatitis C.	Shimoyama Y	Hepatology research : the official journal of the Japan Society of Hepatology	2013	PMID: 23281610
Association study of IL28B: rs12979860 and rs8099917 polymorphisms with SVR in patients infected with chronic HCV genotype 1 to PEG-INF/RBV therapy using systematic meta-analysis.	Luo Y	Gene	2013	PMID: 23142377
Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.	Vidal F	PloS one	2012	PMID: 23133602
Interleukin-28B (IL-28B) single-nucleotide polymorphisms and interferon plus ribavirin treatment outcome in Italian chronically HCV-infected patients.	Riva E	Journal of viral hepatitis	2012	PMID: 22863269
Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus.	Kobayashi M	Journal of gastroenterology	2012	PMID: 22438096
IL28B polymorphisms do not predict response to therapy in chronic hepatitis C with HCV genotype 5.	Antaki N	Gut	2012	PMID: 22345656
Deciphering the interleukin 28B variants that better predict response to pegylated interferon-α and ribavirin therapy in HCV/HIV-1 coinfected patients.	de Castellarnau M	PloS one	2012	PMID: 22328925
Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy.	Liu CH	Antiviral therapy	2012	PMID: 22301466
IL28B polymorphisms associated with therapy response in Chilean chronic hepatitis C patients.	Venegas M	World journal of gastroenterology	2011	PMID: 21987611
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.	Suppiah V	PLoS medicine	2011	PMID: 21931540
Genetic variation in interleukin-28B predicts SVR in hepatitis C genotype 1 Argentine patients treated with PEG IFN and ribavirin.	Ridruejo E	Annals of hepatology	2011	PMID: 21911885
Polymorphism near the IL28B gene in Korean hepatitis C virus-infected patients treated with peg-interferon plus ribavirin.	Lyoo K	Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology	2011	PMID: 21907615
Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy.	Hayashi K	Liver international : official journal of the International Association for the Study of the Liver	2011	PMID: 21745312
Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene.	Toyoda H	Journal of medical virology	2011	PMID: 21739446
IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C.	Chayama K	The Journal of infectious diseases	2011	PMID: 21628662
Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b.	Hashimoto Y	Journal of medical virology	2011	PMID: 21503910
Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation.	Coto-Llerena M	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons	2011	PMID: 21466653
Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.	Lagging M	PloS one	2011	PMID: 21390311
Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation.	Eurich D	Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society	2011	PMID: 21384511
IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection.	Moghaddam A	Hepatology (Baltimore, Md.)	2011	PMID: 21374656
Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b.	Sakamoto N	Journal of medical virology	2011	PMID: 21360545
IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection.	Chen JY	Genes and immunity	2011	PMID: 21346780
Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy.	Hsu CS	Proceedings of the National Academy of Sciences of the United States of America	2011	PMID: 21321200
Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients.	Yu ML	Hepatology (Baltimore, Md.)	2011	PMID: 21254157
Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir.	Suzuki F	Hepatology (Baltimore, Md.)	2011	PMID: 21246582
Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.	Scherzer TM	Journal of hepatology	2011	PMID: 21145807
Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b.	Kawaoka T	Journal of hepatology	2011	PMID: 21112660
Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients.	Sarrazin C	Journal of hepatology	2011	PMID: 21112657
HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy.	Hayes CN	Gut	2011	PMID: 21068134
IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.	Aparicio E	PloS one	2010	PMID: 21048934
Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin.	Akuta N	Hepatology (Baltimore, Md.)	2010	PMID: 20648473
Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C.	Honda M	Gastroenterology	2010	PMID: 20434452
Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.	Rauch A	Gastroenterology	2010	PMID: 20060832
IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.	Suppiah V	Nature genetics	2009	PMID: 19749758
Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.	Tanaka Y	Nature genetics	2009	PMID: 19749757
https://www.pharmgkb.org/clinicalAnnotation/1183888959	-	-	-	-
https://www.pharmgkb.org/clinicalAnnotation/981239773	-	-	-	-
https://www.pharmgkb.org/variant/PA166155435	-	-	-	-
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Text-mined citations for rs8099917 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NC_000019.10:g.39252525T>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs8099917 ...