rs367732440
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1
The NM_006158.5(NEFL):c.207G>A(p.Glu69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,610,704 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
NEFL
NM_006158.5 synonymous
NM_006158.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0570
Genes affected
NEFL (HGNC:7739): (neurofilament light chain) Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the light chain neurofilament protein. Mutations in this gene cause Charcot-Marie-Tooth disease types 1F (CMT1F) and 2E (CMT2E), disorders of the peripheral nervous system that are characterized by distinct neuropathies. A pseudogene has been identified on chromosome Y. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 8-24956309-C-T is Benign according to our data. Variant chr8-24956309-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 417207.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.057 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000295 (45/152318) while in subpopulation AFR AF= 0.00103 (43/41574). AF 95% confidence interval is 0.000789. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.207G>A | p.Glu69= | synonymous_variant | 1/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.207G>A | p.Glu69= | synonymous_variant | 1/4 | 1 | NM_006158.5 | P1 | |
ENST00000607735.2 | n.369C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
NEFL | ENST00000615973.1 | n.413G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000830 AC: 20AN: 241006Hom.: 0 AF XY: 0.0000687 AC XY: 9AN XY: 130990
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1458386Hom.: 0 Cov.: 36 AF XY: 0.0000221 AC XY: 16AN XY: 725070
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GnomAD4 genome AF: 0.000295 AC: 45AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2E Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at