VCV002502287.1 - ClinVar

NM_017460.6(CYP3A4):c.1026+12G>A

Germline

Top reviewed classifications are shown here.

Submission summary:

2 submissions

1 submitter

2 conditions

Reviewed by expert panel

Drug response

Jan 2023 by PharmGKB

for tacrolimus response - Metabolism/PK

Drug response

Jan 2023 by PharmGKB

for fentanyl response - Dosage

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_017460.6(CYP3A4):c.1026+12G>A

Variation ID: 2502287 Accession: VCV002502287.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.1 7: 99763843 (GRCh38) [ NCBI UCSC ] 7: 99361466 (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	May 20, 2023	May 20, 2023	Jan 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_017460.6:c.1026+12G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001202855.3:c.1023+12G>A		intron variant
NC_000007.14:g.99763843C>T
NC_000007.13:g.99361466C>T
NG_008421.1:g.25343G>A
NG_054907.1:g.313C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:99763842:C:T

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.

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

Links

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.
CYP3A4		-	-	GRCh38 GRCh37	16	45
LOC110366355	-	-	-	GRCh38	-	9

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.
tacrolimus response - Metabolism/PK	drug response (1)	reviewed by expert panel	Jan 20, 2023	RCV003228706.3
fentanyl response - Dosage	drug response (1)	reviewed by expert panel	Jan 17, 2023	RCV003228705.3

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: Metabolism/PK (Jan 20, 2023)	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine) Method: curation	tacrolimus response - Metabolism/PK Drug used for Kidney Transplantation , and liver transplantation Affected status: yes Allele origin: germline	PharmGKB Accession: SCV003925526.1 First in ClinVar: May 20, 2023 Last updated: May 20, 2023 Comment: Drug is not necessarily used to treat response condition	Publications: PubMed (11) PubMed: 21635144‚ 22108237‚ 23459029‚ 24189425‚ 24465960‚ 26227094‚ 26228923‚ 28112181‚ 29318894‚ 31401678‚ 31588879 Other databases https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166157345 https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/1451989360 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)
drug response Drug-variant association: Dosage (Jan 17, 2023)	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine) Method: curation	fentanyl response - Dosage Drug used for Pain, Postoperative Affected status: yes Allele origin: germline	PharmGKB Accession: SCV003925525.1 First in ClinVar: May 20, 2023 Last updated: May 20, 2023 Comment: Drug is not necessarily used to treat response condition	Publications: PubMed (6) PubMed: 19784640‚ 21223952‚ 21513075‚ 21535061‚ 25794200‚ 29601950 Other databases https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166157345 https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/1451985380 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)

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:

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
Impact of CYP3A4/5 and ABCB1 polymorphisms on tacrolimus exposure and response in pediatric primary nephrotic syndrome.	Huang L	Pharmacogenomics	2019	PMID: 31588879
CYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria.	Liu H	European journal of clinical pharmacology	2019	PMID: 31401678
Association between MDR(1)/CYP3A4/OPRM(1) gene polymorphisms and the post-caesarean fentanyl analgesic effect on Chinese women.	Zhang J	Gene	2018	PMID: 29601950
Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.	Oetting WS	Pharmacogenomics	2018	PMID: 29318894
IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients.	Liu MZ	Acta pharmacologica Sinica	2017	PMID: 28112181
Interactive effects of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tracrolimus trough concentrations in early postrenal transplant recipients.	Li JL	Pharmacogenomics	2015	PMID: 26228923
The genetic polymorphisms of POR28 and CYP3A53 significantly influence the pharmacokinetics of tacrolimus in Chinese renal transplant recipients.	Zhang JJ	International journal of clinical pharmacology and therapeutics	2015	PMID: 26227094
The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis.	Ren ZY	Pain physician	2015	PMID: 25794200
Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR genetic polymorphisms on tacrolimus metabolism in Chinese renal transplant recipients.	Li CJ	PloS one	2014	PMID: 24465960
Influence of cytochrome P450 (CYP) 3A4*1G polymorphism on the pharmacokinetics of tacrolimus, probability of acute cellular rejection, and mRNA expression level of CYP3A5 rather than CYP3A4 in living-donor liver transplant patients.	Uesugi M	Biological & pharmaceutical bulletin	2013	PMID: 24189425
Effects of CYP3A4 and CYP3A5 polymorphisms on tacrolimus pharmacokinetics in Chinese adult renal transplant recipients: a population pharmacokinetic analysis.	Zuo XC	Pharmacogenetics and genomics	2013	PMID: 23459029
The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recipients.	Birdwell KA	Pharmacogenetics and genomics	2012	PMID: 22108237
Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population.	Dong ZL	Journal of clinical pharmacy and therapeutics	2012	PMID: 21535061
Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients.	Miura M	Pharmacogenomics	2011	PMID: 21635144
Influence of CYP3A53 polymorphism and interaction between CYP3A53 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese patients undergoing gynaecological surgery.	Zhang W	European journal of anaesthesiology	2011	PMID: 21513075
Impact of CYP3A4*1G polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery.	Yuan R	Clinica chimica acta; international journal of clinical chemistry	2011	PMID: 21223952
CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients.	Zhang W	European journal of clinical pharmacology	2010	PMID: 19784640
https://www.pharmgkb.org/clinicalAnnotation/1451985380	-	-	-	-
https://www.pharmgkb.org/clinicalAnnotation/1451989360	-	-	-	-
https://www.pharmgkb.org/variant/PA166157345	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_017460.6(CYP3A4):c.1026+12G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...