2-166042428-T-TAA
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS2
The NM_001165963.4(SCN1A):c.2044-5_2044-4insTT 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 0.00000349 in 1,433,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
SCN1A
NM_001165963.4 splice_region, splice_polypyrimidine_tract, intron
NM_001165963.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.278
Genes affected
SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 2-166042428-T-TAA is Benign according to our data. Variant chr2-166042428-T-TAA is described in ClinVar as [Benign]. Clinvar id is 3019463.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.2044-5_2044-4insTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000674923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.2044-5_2044-4insTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001165963.4 | P4 | ||||
SCN1A-AS1 | ENST00000651574.1 | n.487+6306_487+6307dup | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000219 AC: 5AN: 228492Hom.: 0 AF XY: 0.0000162 AC XY: 2AN XY: 123602
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GnomAD4 exome AF: 0.00000349 AC: 5AN: 1433598Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2AN XY: 713464
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GnomAD4 genome Cov.: 33
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33
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 14, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at