rs3761
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006158.5(NEFL):c.*1107C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,636 control chromosomes in the GnomAD database, including 968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 965 hom., cov: 33)
Exomes 𝑓: 0.17 ( 3 hom. )
Consequence
NEFL
NM_006158.5 3_prime_UTR
NM_006158.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.516
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 8-24951703-G-A is Benign according to our data. Variant chr8-24951703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.*1107C>T | 3_prime_UTR_variant | 4/4 | ENST00000610854.2 | NP_006149.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.*1107C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_006158.5 | ENSP00000482169 | P1 |
Frequencies
GnomAD3 genomes AF: 0.102 AC: 15561AN: 152088Hom.: 966 Cov.: 33
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GnomAD4 exome AF: 0.174 AC: 75AN: 430Hom.: 3 Cov.: 0 AF XY: 0.192 AC XY: 50AN XY: 260
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GnomAD4 genome AF: 0.102 AC: 15559AN: 152206Hom.: 965 Cov.: 33 AF XY: 0.103 AC XY: 7652AN XY: 74410
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Charcot-Marie-Tooth disease, type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at