NM_006158.5:c.1179G>A

Variant names:

• chr8-24953786-C-T
• rs879253927
• NM_006158.5:c.1179G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_006158.5(NEFL):​c.1179G>A​(p.Leu393Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NEFL NM_006158.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP7: Synonymous conserved (PhyloP=2.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEFL	NM_006158.5	MANE Select	c.1179G>A	p.Leu393Leu	synonymous	Exon 3 of 4	NP_006149.2	P07196
	MIR6841	NR_106900.1		n.*10G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEFL	ENST00000610854.2	TSL:1 MANE Select	c.1179G>A	p.Leu393Leu	synonymous	Exon 3 of 4	ENSP00000482169.2	P07196
	NEFL	ENST00000916556.1		c.1179G>A	p.Leu393Leu	synonymous	Exon 3 of 4	ENSP00000586615.1
	MIR6841	ENST00000637129.1	TSL:6	n.*10G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457328 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724294

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108868

Other (OTH) AF: 0.0000166 AC: 1 AN: 60164

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879253927; hg19: chr8-24811300;