8-24951612-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.*1198G>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 0.0818 in 152,566 control chromosomes in the GnomAD database, including 682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (682 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.631

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=-0.59).
• BP6: Variant 8-24951612-C-G is Benign according to our data. Variant chr8-24951612-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 362625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEFL	NM_006158.5	c.*1198G>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.*1198G>C		3_prime_UTR_variant	4/4	1	NM_006158.5	P1

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12470 AN: 152068 Hom.: 682 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.00263 AC: 1 AN: 380 Hom.: 0 Cov.: 0 AF XY: 0.00435 AC XY: 1 AN XY: 230

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0820 AC: 12475 AN: 152186 Hom.: 682 Cov.: 32 AF XY: 0.0789 AC XY: 5868 AN XY: 74408

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0257 Hom.: 13

Bravo AF: 0.0889

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	5.4
Dann	Benign	0.78

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: rs4644268; hg19: chr8-24809125;