8-24952123-C-G

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.*687G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,370 control chromosomes in the GnomAD database, including 24,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (24394 hom., cov: 32)
  • Exomes 𝑓: 0.64 (75 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.137

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=-0.86).
• BP6: Variant 8-24952123-C-G is Benign according to our data. Variant chr8-24952123-C-G is described in ClinVar as [Benign]. Clinvar id is 362632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEFL	NM_006158.5	c.*687G>C		3_prime_UTR_variant	4/4	ENST00000610854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEFL	ENST00000610854.2	c.*687G>C		3_prime_UTR_variant	4/4	1	NM_006158.5	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82900 AN: 151826 Hom.: 24384 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.636 AC: 271 AN: 426 Hom.: 75 Cov.: 0 AF XY: 0.628 AC XY: 162 AN XY: 258

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.546 AC: 82935 AN: 151944 Hom.: 24394 Cov.: 32 AF XY: 0.550 AC XY: 40847 AN XY: 74264

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.546

Alfa AF: 0.574 Hom.: 3174

Bravo AF: 0.539

Asia WGS AF: 0.646 AC: 2241 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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	-0.86
Cadd	Benign	2.6
Dann	Benign	0.68

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: rs2976439; hg19: chr8-24809636; COSMIC: COSV55337561; COSMIC: COSV55337561;