rs3761

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

2

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]

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
NEFLNM_006158.5 linkuse as main transcriptc.*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
NEFLENST00000610854.2 linkuse as main transcriptc.*1107C>T 3_prime_UTR_variant 4/41 NM_006158.5 ENSP00000482169 P1

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15561
AN:
152088
Hom.:
966
Cov.:
33
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:
75
AN:
430
Hom.:
3
Cov.:
0
AF XY:
0.192
AC XY:
50
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.:
33
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Charcot-Marie-Tooth disease, type I Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 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.

Other links and lift over

dbSNP: rs3761; hg19: chr8-24809216; API