rs532240912
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006158.5(NEFL):āc.582A>Cā(p.Glu194Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,603,990 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E194G) has been classified as Uncertain significance.
Frequency
Consequence
NM_006158.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.582A>C | p.Glu194Asp | missense_variant | 1/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.582A>C | p.Glu194Asp | missense_variant | 1/4 | 1 | NM_006158.5 | P1 | |
NEFL | ENST00000615973.1 | n.788A>C | non_coding_transcript_exon_variant | 1/1 | |||||
ENST00000607735.2 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00121 AC: 285AN: 236478Hom.: 7 AF XY: 0.00164 AC XY: 213AN XY: 129978
GnomAD4 exome AF: 0.000557 AC: 809AN: 1451708Hom.: 17 Cov.: 36 AF XY: 0.000836 AC XY: 604AN XY: 722712
GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74454
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, 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 | Sep 09, 2019 | 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 2E Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | NEFL: BS2 - |
NEFL-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at