rs750251152
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4_StrongBP6
The NM_006158.5(NEFL):āc.339G>Cā(p.Gln113His) variant causes a missense change. The variant allele was found at a frequency of 0.000143 in 1,609,980 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. Q113P) has been classified as Likely benign.
Frequency
Consequence
NM_006158.5 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 |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.339G>C | p.Gln113His | missense_variant | 1/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.339G>C | p.Gln113His | missense_variant | 1/4 | 1 | NM_006158.5 | P1 | |
ENST00000607735.2 | n.237C>G | non_coding_transcript_exon_variant | 1/1 | ||||||
NEFL | ENST00000615973.1 | n.545G>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000284 AC: 68AN: 239810Hom.: 0 AF XY: 0.000299 AC XY: 39AN XY: 130520
GnomAD4 exome AF: 0.000145 AC: 211AN: 1457780Hom.: 0 Cov.: 36 AF XY: 0.000155 AC XY: 112AN XY: 724820
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74340
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease type 1F Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at