chr1-204952130-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001005388.3(NFASC):c.215+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,588,814 control chromosomes in the GnomAD database, including 140,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.33 ( 9796 hom., cov: 32)
Exomes 𝑓: 0.42 ( 130968 hom. )
Consequence
NFASC
NM_001005388.3 intron
NM_001005388.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.365
Genes affected
NFASC (HGNC:29866): (neurofascin) This gene encodes an L1 family immunoglobulin cell adhesion molecule with multiple IGcam and fibronectin domains. The protein functions in neurite outgrowth, neurite fasciculation, and organization of the axon initial segment (AIS) and nodes of Ranvier on axons during early development. Both the AIS and nodes of Ranvier contain high densities of voltage-gated Na+ (Nav) channels which are clustered by interactions with cytoskeletal and scaffolding proteins including this protein, gliomedin, ankyrin 3 (ankyrin-G), and betaIV spectrin. This protein links the AIS extracellular matrix to the intracellular cytoskeleton. This gene undergoes extensive alternative splicing, and the full-length nature of some variants has not been determined.[provided by RefSeq, May 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 1-204952130-A-G is Benign according to our data. Variant chr1-204952130-A-G is described in ClinVar as [Benign]. Clinvar id is 1325900.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFASC | NM_001005388.3 | c.215+14A>G | intron_variant | ENST00000339876.11 | |||
NFASC | NM_001160331.2 | c.197+14A>G | intron_variant | ENST00000539706.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFASC | ENST00000339876.11 | c.215+14A>G | intron_variant | 5 | NM_001005388.3 | ||||
NFASC | ENST00000539706.6 | c.197+14A>G | intron_variant | 5 | NM_001160331.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.328 AC: 49872AN: 151950Hom.: 9798 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
49872
AN:
151950
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.374 AC: 92826AN: 248338Hom.: 19076 AF XY: 0.384 AC XY: 51534AN XY: 134094
GnomAD3 exomes
AF:
AC:
92826
AN:
248338
Hom.:
AF XY:
AC XY:
51534
AN XY:
134094
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.418 AC: 601165AN: 1436746Hom.: 130968 Cov.: 25 AF XY: 0.420 AC XY: 300766AN XY: 715908
GnomAD4 exome
AF:
AC:
601165
AN:
1436746
Hom.:
Cov.:
25
AF XY:
AC XY:
300766
AN XY:
715908
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.328 AC: 49880AN: 152068Hom.: 9796 Cov.: 32 AF XY: 0.325 AC XY: 24146AN XY: 74324
GnomAD4 genome
?
AF:
AC:
49880
AN:
152068
Hom.:
Cov.:
32
AF XY:
AC XY:
24146
AN XY:
74324
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
808
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with central and peripheral motor dysfunction Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at