rs3761

chr8-24951703-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.*1107C>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 0.102 in 152,636 control chromosomes in the GnomAD database, including 968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (965 hom., cov: 33)
  • Exomes 𝑓: 0.17 (3 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.516

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=-0.81).
• BP6: Variant 8-24951703-G-A is Benign according to our data. Variant chr8-24951703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEFL	NM_006158.5	c.*1107C>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.*1107C>T		3_prime_UTR_variant	4/4	1	NM_006158.5	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15561 AN: 152088 Hom.: 966 Cov.: 33

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.174 AC: 75 AN: 430 Hom.: 3 Cov.: 0 AF XY: 0.192 AC XY: 50 AN XY: 260

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.102 AC: 15559 AN: 152206 Hom.: 965 Cov.: 33 AF XY: 0.103 AC XY: 7652 AN XY: 74410

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.103

Alfa AF: 0.126 Hom.: 274

Bravo AF: 0.0907

Asia WGS AF: 0.0630 AC: 219 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	-0.81
Cadd	Benign	3.8
Dann	Benign	0.59

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: rs3761; hg19: chr8-24809216;