17-31374114-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001042492.3(NF1):c.8479G>T(p.Ala2827Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A2827T) has been classified as Likely benign.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.8479G>T | p.Ala2827Ser | missense_variant | 58/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.8416G>T | p.Ala2806Ser | missense_variant | 57/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.8479G>T | p.Ala2827Ser | missense_variant | 58/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251284Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135802
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727184
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74474
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2022 | In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2016 | The p.A2827S variant (also known as c.8479G>T), located in coding exon 58 of the NF1 gene, results from a G to T substitution at nucleotide position 8479. The alanine at codon 2827 is replaced by serine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs199878086. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.94% (1/106) African-American SW alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied, having been observed in 0%African American allelesand 0.01% (1/8600) European American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.009% (greater than 110000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.A2827S remains unclear.​ - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at