rs60547413
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006158.5(NEFL):c.1212C>T(p.Ser404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,644 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 2 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]
MIR6841 (HGNC:50070): (microRNA 6841) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 8-24953753-G-A is Benign according to our data. Variant chr8-24953753-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 66673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-24953753-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.057 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000179 (261/1461490) while in subpopulation SAS AF= 0.00177 (153/86240). AF 95% confidence interval is 0.00154. There are 2 homozygotes in gnomad4_exome. There are 179 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEFL | NM_006158.5 | c.1212C>T | p.Ser404= | synonymous_variant | 3/4 | ENST00000610854.2 | |
MIR6841 | NR_106900.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.1212C>T | p.Ser404= | synonymous_variant | 3/4 | 1 | NM_006158.5 | P1 | |
MIR6841 | ENST00000637129.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152154Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
17
AN:
152154
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000354 AC: 88AN: 248406Hom.: 1 AF XY: 0.000430 AC XY: 58AN XY: 134798
GnomAD3 exomes
AF:
AC:
88
AN:
248406
Hom.:
AF XY:
AC XY:
58
AN XY:
134798
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000179 AC: 261AN: 1461490Hom.: 2 Cov.: 32 AF XY: 0.000246 AC XY: 179AN XY: 726976
GnomAD4 exome
AF:
AC:
261
AN:
1461490
Hom.:
Cov.:
32
AF XY:
AC XY:
179
AN XY:
726976
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74324
GnomAD4 genome
?
AF:
AC:
17
AN:
152154
Hom.:
Cov.:
33
AF XY:
AC XY:
9
AN XY:
74324
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 30, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | literature only | Inherited Neuropathy Consortium | - | - - |
not provided Benign:1Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | NEFL: BP4, BP7 - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
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. - |
Charcot-Marie-Tooth disease type 2E Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at