rs79736124

Variant names:

• chr8-24951710-G-A
• rs79736124
• NM_006158.5:c.*1100C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-24951710-G-A
• chr8-24951710-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006158.5(NEFL):​c.*1100C>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 0.0384 in 152,618 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (155 hom., cov: 32)
  • Exomes 𝑓: 0.079 (0 hom.)
• Consequence: NEFL NM_006158.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.43

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-24951710-G-A is Benign according to our data. Variant chr8-24951710-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-24951710-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest population allele frequency = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEFL	NM_006158.5	c.*1100C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000610854.2	NP_006149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEFL	ENST00000610854.2	c.*1100C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_006158.5	ENSP00000482169.2

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5821 AN: 152068 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0787 AC: 34 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.0885 AC XY: 23 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0798 AC: 34 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0383 AC: 5824 AN: 152186 Hom.: 155 Cov.: 32 AF XY: 0.0392 AC XY: 2918 AN XY: 74404

African (AFR) AF: 0.0237 AC: 983 AN: 41526

American (AMR) AF: 0.0366 AC: 559 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4820

European-Finnish (FIN) AF: 0.0965 AC: 1021 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0411 AC: 2792 AN: 68008

Other (OTH) AF: 0.0535 AC: 113 AN: 2114

Alfa AF: 0.0391 Hom.: 173

Bravo AF: 0.0341

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Charcot-Marie-Tooth disease, type I Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		1.4

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

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Other links and lift over

dbSNP: rs79736124; hg19: chr8-24809223;