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NM_003977.4(AIP):c.47G>A (p.Arg16His)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(5);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Nov 4, 2021)
Last evaluated:
Nov 3, 2021
Accession:
VCV000041184.12
Variation ID:
41184
Description:
single nucleotide variant
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NM_003977.4(AIP):c.47G>A (p.Arg16His)

Allele ID
49606
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11q13.2
Genomic location
11: 67483205 (GRCh38) GRCh38 UCSC
11: 67250676 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_460:g.5172G>A
LRG_460t1:c.47G>A
NC_000011.10:g.67483205G>A
... more HGVS
Protein change
R16H
Other names
-
Canonical SPDI
NC_000011.10:67483204:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (A)

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00254
The Genome Aggregation Database (gnomAD) 0.00296
The Genome Aggregation Database (gnomAD), exomes 0.00197
Exome Aggregation Consortium (ExAC) 0.00196
1000 Genomes Project 0.00060
Trans-Omics for Precision Medicine (TOPMed) 0.00197
Links
ClinGen: CA344116
dbSNP: rs145047094
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, multiple submitters, no conflicts Mar 4, 2021 RCV000893230.5
Likely benign 1 criteria provided, single submitter Mar 28, 2019 RCV000560928.2
Likely benign 1 criteria provided, single submitter May 20, 2021 RCV001554284.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Nov 3, 2021 RCV000034083.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
AIP - - GRCh38
GRCh37
378 395

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Dec 07, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001037150.3
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(May 20, 2021)
criteria provided, single submitter
Method: clinical testing
Pituitary adenoma, familial isolated
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV001775518.1
Submitted: (Aug 07, 2021)
Evidence details
Likely benign
(Mar 04, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001827081.1
Submitted: (Sep 02, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 19366855, 27267386, … (more)
Likely benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Somatotroph adenoma
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000373570.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Mar 28, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000664980.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (14)
Comment:
Does not segregate with disease in family study (genes with incomplete penetrance);Other data supporting benign classification
Uncertain significance
(Nov 03, 2021)
criteria provided, single submitter
Method: clinical testing
Somatotroph adenoma
Allele origin: germline
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009990.1
Submitted: (Nov 04, 2021)
Evidence details
unknown
(Jun 21, 2012)
no assertion criteria provided
Method: curation
AIP-Related Familial Isolated Pituitary Adenomas
Allele origin: not provided
GeneReviews
Accession: SCV000058013.2
Submitted: (Mar 26, 2013)
Evidence details
Comment:
Converted during submission to Uncertain significance.

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
<i>AIP</i> Familial Isolated Pituitary Adenomas Korbonits M - 2020 PMID: 22720333
Aryl Hydrocarbon Receptor-Interacting Protein (AIP) N-Terminus Gene Mutations Identified in Pituitary Adenoma Patients Alter Protein Stability and Function. Formosa R Hormones & cancer 2017 PMID: 28255869
An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Dinesen PT Endocrinology, diabetes & metabolism case reports 2015 PMID: 25614825
Low rate of germline AIP mutations in patients with apparently sporadic pituitary adenomas before the age of 40: a single-centre adult cohort. Preda V European journal of endocrinology 2014 PMID: 25184284
Should aip gene screening be recommended in family members of FIPA patients with R16H variant? Zatelli MC Pituitary 2013 PMID: 22915287
Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients. Cazabat L The Journal of clinical endocrinology and metabolism 2012 PMID: 22319033
High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. Tichomirowa MA European journal of endocrinology 2011 PMID: 21753072
Familial isolated pituitary adenomas: from genetics to therapy. Guaraldi F Clinical and translational science 2011 PMID: 21348957
Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Igreja S Human mutation 2010 PMID: 20506337
Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition. Vierimaa O Journal of endocrinological investigation 2009 PMID: 19474519
Aryl hydrocarbon receptor interacting protein gene (AIP) mutations are rare in patients with hormone secreting or non-secreting pituitary adenomas. Buchbinder S Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2008 PMID: 18484068
Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. Cazabat L European journal of endocrinology 2007 PMID: 17609395
Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. Daly AF The Journal of clinical endocrinology and metabolism 2007 PMID: 17244780
Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers. Georgitsi M British journal of cancer 2007 PMID: 17242703
Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Vierimaa O Science (New York, N.Y.) 2006 PMID: 16728643

Text-mined citations for rs145047094...

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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 Nov 06, 2021