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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 1F

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2E

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 2B5

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId is 362628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest population allele frequency = 0.0787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEFL	NM_006158.5	MANE Select	c.*1100C>T		3_prime_UTR	Exon 4 of 4	NP_006149.2	P07196

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEFL	ENST00000610854.2	TSL:1 MANE Select	c.*1100C>T		3_prime_UTR	Exon 4 of 4	ENSP00000482169.2	P07196
	NEFL	ENST00000916556.1		c.*1100C>T		3_prime_UTR	Exon 4 of 4	ENSP00000586615.1

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease, type I (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs79736124; hg19: chr8-24809223;