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NM_001287174.2(ABCC8):c.3992-9G>A

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 19, 2018
Accession:
VCV000009088.2
Variation ID:
9088
Description:
single nucleotide variant
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NM_001287174.2(ABCC8):c.3992-9G>A

Allele ID
24127
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.1
Genomic location
11: 17397055 (GRCh38) GRCh38 UCSC
11: 17418602 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000011.10:g.17397055C>T
NC_000011.9:g.17418602C>T
NM_000352.5:c.3989-9G>A
... more HGVS
Protein change
-
Other names
3992-9G>A
IVS32, G-A, -9, EXON ALPHA DEL
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00013
Exome Aggregation Consortium (ExAC) 0.00018
The Genome Aggregation Database (gnomAD), exomes 0.00033
The Genome Aggregation Database (gnomAD) 0.00003
1000 Genomes Project 0.00020
Links
dbSNP: rs151344623
ClinGen: CA233276
OMIM: 600509.0002
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 criteria provided, multiple submitters, no conflicts Dec 19, 2018 RCV000144995.3
Pathogenic 2 criteria provided, single submitter Nov 9, 2015 RCV000009656.6
Pathogenic 1 criteria provided, single submitter Jun 5, 2017 RCV000590487.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ABCC8 - - GRCh38
GRCh37
389 418

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 23, 2013)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal unknown)
Allele origin: germline
Genetic Services Laboratory, University of Chicago
Accession: SCV000192031.1
Submitted: (Sep 11, 2014)
Evidence details
Pathogenic
(Nov 09, 2015)
criteria provided, single submitter
Method: clinical testing
Persistent hyperinsulinemic hypoglycemia of infancy
Allele origin: unknown
Counsyl
Accession: SCV000678147.1
Submitted: (Jun 22, 2017)
Evidence details
Publications
PubMed (16)
Pathogenic
(Jun 05, 2017)
criteria provided, single submitter
Method: clinical testing
Familial hyperinsulinism
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000696590.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: The ABCC8 variant, c.3989-9G>A (alternatively also known as 3992-9G>A) involves the alteration of a non-conserved intronic nucleotide in intron 32. Mutation taster predicts ... (more)
Pathogenic
(Apr 11, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000612213.2
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (25)
Pathogenic
(Jun 13, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000229594.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/em...
Pathogenic
(Dec 19, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV000954424.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change falls in intron 32 of the ABCC8 gene. It does not directly change the encoded amino acid sequence of the ABCC8 protein. ... (more)
Pathogenic
(Oct 07, 2015)
no assertion criteria provided
Method: clinical testing
Not provided
Allele origin: germline
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia
Accession: SCV000256803.1
Submitted: (Oct 28, 2015)
Comment:
Clinical Testing
Evidence details
Pathogenic
(Jan 01, 1999)
no assertion criteria provided
Method: literature only
HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 1
Allele origin: germline
OMIM
Accession: SCV000029874.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)

Citations for this variant

Title Author Journal Year Link
Diagnosis of ABCC8 Congenital Hyperinsulinism of Infancy in a 20-Year-Old Man Evaluated for Factitious Hypoglycemia. Gutgold A The Journal of clinical endocrinology and metabolism 2017 PMID: 27754802
Expanding preconception carrier screening for the Jewish population using high throughput microfluidics technology and next generation sequencing. Gal M BMC medical genomics 2016 PMID: 27175728
Clinical and molecular data from 61 Brazilian cases of Congenital Hyperinsulinemic Hypoglycemia. Del Roio Liberatore R Jr Diabetology & metabolic syndrome 2015 PMID: 25972930
Phenotypic heterogeneity in monogenic diabetes: the clinical and diagnostic utility of a gene panel-based next-generation sequencing approach. Alkorta-Aranburu G Molecular genetics and metabolism 2014 PMID: 25306193
Clinical and genetic evaluation of patients with KATP channel mutations from the German registry for congenital hyperinsulinism. Mohnike K Hormone research in paediatrics 2014 PMID: 24401662
Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Kapoor RR European journal of endocrinology 2013 PMID: 23345197
Congenital hyperinsulinism: marked clinical heterogeneity in siblings with identical mutations in the ABCC8 gene. Kapoor RR Clinical endocrinology 2012 PMID: 21851374
ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Glaser B Genetics in medicine : official journal of the American College of Medical Genetics 2011 PMID: 21716120
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism. Bellanné-Chantelot C Journal of medical genetics 2010 PMID: 20685672
Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases. Scott SA Human mutation 2010 PMID: 20672374
Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Flanagan SE Human mutation 2009 PMID: 18767144
Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon. Mohnike K Hormone research 2008 PMID: 18493152
Glucose intolerance and diabetes are observed in the long-term follow-up of nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene. Gussinyer M Diabetes care 2008 PMID: 18339976
Genotype-phenotype associations in patients with severe hyperinsulinism of infancy. Greer RM Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2007 PMID: 17378627
Protein-sensitive hypoglycemia without leucine sensitivity in hyperinsulinism caused by K(ATP) channel mutations. Fourtner SH The Journal of pediatrics 2006 PMID: 16860127
Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI). Fernández-Marmiesse A Human mutation 2006 PMID: 16429405
Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. Suchi M Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2006 PMID: 16357843
Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes. Henwood MJ The Journal of clinical endocrinology and metabolism 2005 PMID: 15562009
Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity. Tornovsky S The Journal of clinical endocrinology and metabolism 2004 PMID: 15579781
Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor. Magge SN The Journal of clinical endocrinology and metabolism 2004 PMID: 15356046
Preoperative evaluation of infants with focal or diffuse congenital hyperinsulinism by intravenous acute insulin response tests and selective pancreatic arterial calcium stimulation. Stanley CA The Journal of clinical endocrinology and metabolism 2004 PMID: 14715863
Histopathology of congenital hyperinsulinism: retrospective study with genotype correlations. Suchi M Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2003 PMID: 14692646
Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor. Thornton PS Diabetes 2003 PMID: 12941782
Compound heterozygosity for the common sulfonylurea receptor mutations can cause mild diazoxide-sensitive hyperinsulinism. Dekel B Clinical pediatrics 2002 PMID: 11999683
Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. Grimberg A Diabetes 2001 PMID: 11272143
Beta-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Kassem SA Diabetes 2000 PMID: 10923633
Suppression of insulin oversecretion by subcutaneous recombinant human insulin-like growth factor I in children with congenital hyperinsulinism due to defective beta-cell sulfonylurea receptor. Katz LE The Journal of clinical endocrinology and metabolism 1999 PMID: 10487673
Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism. Glaser B Human mutation 1999 PMID: 10447255
Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy. Shyng SL Diabetes 1998 PMID: 9648840
Genetic heterogeneity in familial hyperinsulinism. Nestorowicz A Human molecular genetics 1998 PMID: 9618169
Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews. Nestorowicz A Human molecular genetics 1996 PMID: 8923011
Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Thomas PM Science (New York, N.Y.) 1995 PMID: 7716548
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCC8 - - - -

Record last updated Oct 27, 2019