chr8-24951554-C-T

Position:

• chr8-24951554-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006158.5(NEFL):​c.*1256G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,232 control chromosomes in the GnomAD database, including 47,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47428 hom., cov: 32)
  • Exomes 𝑓: 0.83 (55 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-24951554-C-T is Benign according to our data. Variant chr8-24951554-C-T is described in ClinVar as [Benign]. Clinvar id is 362624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEFL	NM_006158.5	c.*1256G>A		3_prime_UTR_variant	4/4	ENST00000610854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEFL	ENST00000610854.2	c.*1256G>A		3_prime_UTR_variant	4/4	1	NM_006158.5	P1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118515 AN: 151946 Hom.: 47400 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.827 AC: 139 AN: 168 Hom.: 55 Cov.: 0 AF XY: 0.836 AC XY: 92 AN XY: 110

Gnomad4 FIN exome AF: 0.829

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.780 AC: 118598 AN: 152064 Hom.: 47428 Cov.: 32 AF XY: 0.780 AC XY: 57986 AN XY: 74336

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.795

Alfa AF: 0.852 Hom.: 90778

Bravo AF: 0.773

Asia WGS AF: 0.749 AC: 2606 AN: 3478

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	7.1
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2979704; hg19: chr8-24809067; COSMIC: COSV55337552; COSMIC: COSV55337552;