8-24951710-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006158.5(NEFL):c.*1100C>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 0.0384 in 152,618 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (155 hom., cov: 32)
  • Exomes 𝑓: 0.079 (0 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-24951710-G-A is Benign according to our data. Variant chr8-24951710-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362628.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-24951710-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest population allele frequency = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEFL	NM_006158.5	c.*1100C>T		3_prime_UTR_variant	4/4	ENST00000610854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEFL	ENST00000610854.2	c.*1100C>T		3_prime_UTR_variant	4/4	1	NM_006158.5	P1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5821 AN: 152068 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0787 AC: 34 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.0885 AC XY: 23 AN XY: 260

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0383 AC: 5824 AN: 152186 Hom.: 155 Cov.: 32 AF XY: 0.0392 AC XY: 2918 AN XY: 74404

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0406 Hom.: 31

Bravo AF: 0.0341

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease, type I Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.7
Dann	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs79736124; hg19: chr8-24809223;