rs7538403
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001005388.3(NFASC):c.536-851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 152,142 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.014 ( 44 hom., cov: 32)
Consequence
NFASC
NM_001005388.3 intron
NM_001005388.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.148
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2129/152142) while in subpopulation AFR AF= 0.0483 (2007/41514). AF 95% confidence interval is 0.0466. There are 44 homozygotes in gnomad4. There are 1017 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 44 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFASC | NM_001005388.3 | c.536-851G>A | intron_variant | ENST00000339876.11 | |||
NFASC | NM_001160331.2 | c.518-851G>A | intron_variant | ENST00000539706.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFASC | ENST00000339876.11 | c.536-851G>A | intron_variant | 5 | NM_001005388.3 | ||||
NFASC | ENST00000539706.6 | c.518-851G>A | intron_variant | 5 | NM_001160331.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0140 AC: 2124AN: 152026Hom.: 43 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0140 AC: 2129AN: 152142Hom.: 44 Cov.: 32 AF XY: 0.0137 AC XY: 1017AN XY: 74370
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ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at