17-31349086-CTTGTTTGTTTGTTTGT-CTTGTTTGTTTGT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001042492.3(NF1):c.7190-11_7190-8del variant causes a intron change. The variant allele was found at a frequency of 0.0057 in 1,541,198 control chromosomes in the GnomAD database, including 318 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 165 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 153 hom. )
Consequence
NF1
NM_001042492.3 intron
NM_001042492.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.75
Genes affected
NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-31349086-CTTGT-C is Benign according to our data. Variant chr17-31349086-CTTGT-C is described in ClinVar as [Benign]. Clinvar id is 226852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31349086-CTTGT-C is described in Lovd as [Benign]. Variant chr17-31349086-CTTGT-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.7190-11_7190-8del | intron_variant | ENST00000358273.9 | |||
NF1 | NM_000267.3 | c.7127-11_7127-8del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.7190-11_7190-8del | intron_variant | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0254 AC: 3856AN: 151948Hom.: 164 Cov.: 32
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GnomAD3 exomes AF: 0.00818 AC: 1265AN: 154686Hom.: 44 AF XY: 0.00635 AC XY: 519AN XY: 81712
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GnomAD4 exome AF: 0.00355 AC: 4927AN: 1389136Hom.: 153 AF XY: 0.00310 AC XY: 2128AN XY: 686016
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 02, 2015 | c.7190-11_7190-8delGTTT (HGVS nomenclature: c.7190-31_7190-28[5]) in intron 48 o f NF1: This variant is not expected to have clinical significance because it has been identified in 10.6% (312/2980) of African chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; rs149197458). This varian t is not predicted to impact splicing. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2018 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 16, 2017 | Variant summary: The NF1 c.7127-11_7127-8delGTTT variant involves the deletion of four intronic nucleotides in a six (GTTT) repeat region. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant, listed as 17:29676104 CTTGT / Cin the ExAC control database, was found in 444/23188 control chromosomes (19 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.104698 (312/2980). This frequency is about 502 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, the variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 12, 2021 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at