VCV000422739.10 - ClinVar

NM_001042492.3(NF1):c.6705-17G>A

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Pathogenic (2); Likely pathogenic (1); Uncertain significance (2)

5 out of 5 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001042492.3(NF1):c.6705-17G>A

Variation ID: 422739 Accession: VCV000422739.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q11.2 17: 31338008 (GRCh38) [ NCBI UCSC ] 17: 29665026 (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	Apr 29, 2017	Feb 15, 2026	Jun 30, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001042492.3:c.6705-17G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_000267.4:c.6642-17G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000017.11:g.31338008G>A
NC_000017.10:g.29665026G>A
NG_009018.1:g.248032G>A
LRG_214:g.248032G>A
LRG_214t1:c.6642-17G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:31338007:G:A

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

ClinGen: CA16620373 dbSNP: rs1064795966 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.
NF1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	17161	17729

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.
not provided	Uncertain significance (1)	criteria provided, single submitter	Nov 10, 2016	RCV000480830.1
Neurofibromatosis, type 1	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Jun 30, 2023	RCV000660102.13

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Nov 01, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Neurofibromatosis, type 1	Center for Human Genetics, Inc, Center for Human Genetics, Inc Accession: SCV000782083.1 First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Nov 10, 2016) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not provided	GeneDx Accession: SCV000572283.5 First in ClinVar: Apr 29, 2017 Last updated: Apr 29, 2017	Comment: show This variant is denoted NF1 c.6642-17G>A or IVS43-17G>A and consists of a G>A nucleotide substitution at the -17 position of intron 43 of the NF1 gene. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. In silico models are uninformative, and in the absence of RNA or functional studies, the actual effect of this variant is unknown. NF1 c.6642-17G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The guanine (G) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether NF1 c.6642-17G>A is pathogenic or benign. We consider it to be a variant of uncertain significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Jan 20, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Neurofibromatosis, type 1	Institute of Human Genetics, Medical University Innsbruck Accession: SCV001250657.1 First in ClinVar: May 19, 2020 Last updated: May 19, 2020	Publications: DOI: 10.1002/humu.24005 DOI: 10.1002/humu.24005 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Jan 20, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Neurofibromatosis, type 1	UAB Medical Genomics Laboratory, UAB Medicine Accession: SCV001167393.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020	Publications: PubMed (1) PubMed: 32126153 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Jun 30, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Neurofibromatosis, type 1	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003471669.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 15, 2026	Publications: PubMed (1) PubMed: 32126153 Comment: show ClinVar contains an entry for this variant (Variation ID: 422739). This sequence change falls in intron 43 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis, type 1 (PMID: 32126153). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (PMID: 32126153). 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant is denoted NF1 c.6642-17G>A or IVS43-17G>A and consists of a G>A nucleotide substitution at the -17 position of intron 43 of the NF1 gene. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. In silico models are uninformative, and in the absence of RNA or functional studies, the actual effect of this variant is unknown. NF1 c.6642-17G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The guanine (G) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether NF1 c.6642-17G>A is pathogenic or benign. We consider it to be a variant of uncertain significance.

Comment:

ClinVar contains an entry for this variant (Variation ID: 422739). This sequence change falls in intron 43 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis, type 1 (PMID: 32126153). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (PMID: 32126153). 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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
AG-exclusion zone revisited: Lessons to learn from 91 intronic NF1 3' splice site mutations outside the canonical AG-dinucleotides.	Wimmer K	Human mutation	2020	PMID: 32126153

Text-mined citations for rs1064795966 ...

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 Apr 13, 2026