Variant chr8-24951703-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.516

Variant links:

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]

NEFL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
NEFL	NM_006158.5 linkuse as main transcript	c.*1107C>T		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 linkuse as main transcript	c.*1107C>T		3_prime_UTR_variant	4/4	1	NM_006158.5	ENSP00000482169	P1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15561

AN:

152088

Hom.:

966

Cov.:

show subpopulations

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:

AN:

430

Hom.:

Cov.:

AF XY:

0.192

AC XY:

AN XY:

260

show subpopulations

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.:

AF XY:

0.103

AC XY:

7652

AN XY:

74410

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over