rs59251406
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001165963.4(SCN1A):c.2176+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,609,914 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.035 ( 313 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 308 hom. )
Consequence
SCN1A
NM_001165963.4 intron
NM_001165963.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.341
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 2-166042275-T-C is Benign according to our data. Variant chr2-166042275-T-C is described in ClinVar as [Benign]. Clinvar id is 93637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-166042275-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.2176+17A>G | intron_variant | ENST00000674923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.2176+17A>G | intron_variant | NM_001165963.4 | P4 | ||||
SCN1A-AS1 | ENST00000651574.1 | n.487+6145T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0352 AC: 5358AN: 152104Hom.: 310 Cov.: 32
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GnomAD3 exomes AF: 0.00925 AC: 2296AN: 248300Hom.: 143 AF XY: 0.00648 AC XY: 869AN XY: 134062
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GnomAD4 exome AF: 0.00362 AC: 5281AN: 1457692Hom.: 308 Cov.: 30 AF XY: 0.00309 AC XY: 2236AN XY: 724704
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GnomAD4 genome ? AF: 0.0353 AC: 5370AN: 152222Hom.: 313 Cov.: 32 AF XY: 0.0341 AC XY: 2537AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 30, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at