8-24951927-C-G

Position:

• chr8-24951927-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.*883G>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 0.0177 in 152,450 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (0 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.411

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=-0.82).
• BP6: Variant 8-24951927-C-G is Benign according to our data. Variant chr8-24951927-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 362629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEFL	NM_006158.5	c.*883G>C		3_prime_UTR_variant	4/4	ENST00000610854.2	NP_006149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEFL	ENST00000610854.2	c.*883G>C		3_prime_UTR_variant	4/4	1	NM_006158.5	ENSP00000482169	P1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2683 AN: 152116 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00637

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00463 AC: 1 AN: 216 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 138

Gnomad4 FIN exome AF: 0.00476

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0177 AC: 2696 AN: 152234 Hom.: 35 Cov.: 32 AF XY: 0.0180 AC XY: 1343 AN XY: 74426

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00637

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0103 Hom.: 2

Bravo AF: 0.0188

Asia WGS AF: 0.0530 AC: 184 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.52

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: rs76387248; hg19: chr8-24809440;