chr17-31327700-A-G
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1BP4BS2_Supporting
The NM_001042492.3(NF1):c.5470A>G(p.Ile1824Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1824S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
Publications
- neurofibromatosis type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
- neurofibromatosis-Noonan syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
- Moyamoya diseaseInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- hereditary pheochromocytoma-paragangliomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251376 AF XY: 0.0000294 show subpopulations
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727248 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74318 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1Benign:1
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not specified Uncertain:1
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not provided Uncertain:1
In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27153395, 29684080) -
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
The p.I1803V variant (also known as c.5407A>G), located in coding exon 37 of the NF1 gene, results from an A to G substitution at nucleotide position 5407. The isoleucine at codon 1803 is replaced by valine, an amino acid with highly similar properties. This variant has been identified in at least one patient with a personal and family history of breast and/or ovarian cancer (Maxwell KN et al. Am J Hum Genet, 2016 May;98:801-817). In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at