chr8-24952882-G-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_006158.5(NEFL):c.1560C>A(p.Thr520=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000709 in 1,608,136 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 Benign (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 2 hom. )
Consequence
NEFL
NM_006158.5 synonymous
NM_006158.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.595
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 -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 8-24952882-G-T is Benign according to our data. Variant chr8-24952882-G-T is described in ClinVar as [Benign]. Clinvar id is 66679.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.595 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000987 (15/152026) while in subpopulation EAS AF= 0.0029 (15/5166). AF 95% confidence interval is 0.00179. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 33. 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.1560C>A | p.Thr520= | synonymous_variant | 4/4 | ENST00000610854.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEFL | ENST00000610854.2 | c.1560C>A | p.Thr520= | synonymous_variant | 4/4 | 1 | NM_006158.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000987 AC: 15AN: 151906Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000273 AC: 68AN: 249280Hom.: 2 AF XY: 0.000222 AC XY: 30AN XY: 135248
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GnomAD4 exome AF: 0.0000680 AC: 99AN: 1456110Hom.: 2 Cov.: 28 AF XY: 0.0000607 AC XY: 44AN XY: 724700
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GnomAD4 genome AF: 0.0000987 AC: 15AN: 152026Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74316
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2E Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Computational scores
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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