rs747649993
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001165963.4(SCN1A):c.4582-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001165963.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.4582-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000674923.1 | |||
LOC102724058 | NR_110598.1 | n.176-21194G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.4582-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001165963.4 | P4 | ||||
SCN1A-AS1 | ENST00000651574.1 | n.193-21194G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151942Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460318Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726500
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151942Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74196
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2022 | Reported previously as IVS 24-3T>C in an individual with intractable epilepsy; segregation analysis was not performed (Wang et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 29408779, 23195492) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 31, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at