NM_001042492.3(NF1):c.7063-4A>G AND Neurofibromatosis, type 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 22, 2020
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:: RCV001093651.8

Allele description [Variation Report for NM_001042492.3(NF1):c.7063-4A>G]

NM_001042492.3(NF1):c.7063-4A>G

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.7063-4A>G

HGVS:

NC_000017.11:g.31343005A>G
NG_009018.1:g.253029A>G
NM_000267.3:c.7000-4A>G
NM_001042492.3:c.7063-4A>GMANE SELECT
LRG_214t1:c.7000-4A>G
LRG_214:g.253029A>G
NC_000017.10:g.29670023A>G

Links:

dbSNP: rs749805168

NCBI 1000 Genomes Browser:

rs749805168

Molecular consequence:

NM_000267.3:c.7000-4A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001042492.3:c.7063-4A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Neurofibromatosis, type 1 (NF1)
Synonyms:: NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001250661	Institute of Human Genetics, Medical University Innsbruck	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 20, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001512166	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 22, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17311297, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001250661

Institute of Human Genetics, Medical University Innsbruck

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 20, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001512166

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 22, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5' splice-site disruption.

Wimmer K, Roca X, Beiglböck H, Callens T, Etzler J, Rao AR, Krainer AR, Fonatsch C, Messiaen L.

Hum Mutat. 2007 Jun;28(6):599-612.

PubMed [citation]

PMID:: 17311297

See all PubMed Citations (3)

Details of each submission

From Institute of Human Genetics, Medical University Innsbruck, SCV001250661.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001512166.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 46 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is present in population databases (rs749805168, ExAC 0.009%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 17311297).

#	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: Sep 29, 2024

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