NM_000492.4(CFTR):c.2280G>A (p.Thr760=) AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 28, 2019
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000781288.12

Allele description [Variation Report for NM_000492.4(CFTR):c.2280G>A (p.Thr760=)]

NM_000492.4(CFTR):c.2280G>A (p.Thr760=)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.2280G>A (p.Thr760=)

HGVS:

NC_000007.14:g.117592447G>A
NG_016465.4:g.131664G>A
NM_000492.4:c.2280G>AMANE SELECT
NP_000483.3:p.Thr760=
NP_000483.3:p.Thr760=
LRG_663t1:c.2280G>A
LRG_663:g.131664G>A
LRG_663p1:p.Thr760=
NC_000007.13:g.117232501G>A
NM_000492.3:c.2280G>A

Links:

dbSNP: rs138634146

NCBI 1000 Genomes Browser:

rs138634146

Molecular consequence:

NM_000492.4:c.2280G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000919201	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Aug 28, 2019)	germline	clinical testing	Citation Link,
SCV001160049	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Oct 31, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000919201

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Aug 28, 2019)

germline

clinical testing

Citation Link,

SCV001160049

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Oct 31, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919201.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001160049.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The CFTR c.2280G>A; p.Thr760Thr variant (rs138634146) is reported in the literature in a single individual affected with chronic pancreatitis (Midha 2010). This variant is observed on only 10 chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. This is a synonymous variant in a weakly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant does not alter splicing. When this variant was transfected into cultured bronchial epithelial cells (CFBE41o-) derived from a CF patient homozygous for p.Phe508del, expression analyses suggested the p.Thr760Thr variant led to a reduction in CFTR mRNA, although the amount of CFTR protein was within normal parameters for the cell type (Kirchner 2017). Due to limited information, the clinical significance of the p.Thr760Thr variant is uncertain at this time. References: Kirchner S et al. Alteration of protein function by a silent polymorphism linked to tRNA abundance. PLoS Biol. 2017 May 16;15(5):e2000779. Midha S et al. Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations. Gut. 2010 Jun;59(6):800-7.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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