chr2-166406387-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_002976.4(SCN7A):c.4242G>A(p.Val1414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,612,998 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 4 hom. )
Consequence
SCN7A
NM_002976.4 synonymous
NM_002976.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.102
Genes affected
SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 2-166406387-C-T is Benign according to our data. Variant chr2-166406387-C-T is described in ClinVar as [Benign]. Clinvar id is 737372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.102 with no splicing effect.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN7A | NM_002976.4 | c.4242G>A | p.Val1414= | synonymous_variant | 26/26 | ENST00000643258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN7A | ENST00000643258.1 | c.4242G>A | p.Val1414= | synonymous_variant | 26/26 | NM_002976.4 | P1 | ||
SCN7A | ENST00000441411.2 | c.4242G>A | p.Val1414= | synonymous_variant | 25/25 | 1 | P1 | ||
SCN7A | ENST00000424326.5 | c.*2047G>A | 3_prime_UTR_variant, NMD_transcript_variant | 26/26 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00366 AC: 556AN: 151904Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000920 AC: 228AN: 247808Hom.: 1 AF XY: 0.000662 AC XY: 89AN XY: 134416
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GnomAD4 exome AF: 0.000370 AC: 540AN: 1460976Hom.: 4 Cov.: 33 AF XY: 0.000307 AC XY: 223AN XY: 726790
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
SCN7A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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