2-166203939-A-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001365536.1(SCN9A):c.4774+16T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,446,268 control chromosomes in the GnomAD database, including 549,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.89 ( 60405 hom., cov: 33)
Exomes 𝑓: 0.87 ( 489277 hom. )
Consequence
SCN9A
NM_001365536.1 intron
NM_001365536.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0760
Genes affected
SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]
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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=-0.82).
BP6
?
Variant 2-166203939-A-T is Benign according to our data. Variant chr2-166203939-A-T is described in ClinVar as [Benign]. Clinvar id is 258888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-166203939-A-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.4774+16T>A | intron_variant | ENST00000642356.2 | |||
SCN1A-AS1 | NR_110260.1 | n.611+4121A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.4774+16T>A | intron_variant | NM_001365536.1 | P1 | ||||
SCN1A-AS1 | ENST00000651574.1 | n.1289+4121A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.891 AC: 135255AN: 151834Hom.: 60362 Cov.: 33
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GnomAD3 exomes AF: 0.883 AC: 158939AN: 179950Hom.: 70302 AF XY: 0.880 AC XY: 85274AN XY: 96918
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GnomAD4 exome AF: 0.869 AC: 1124794AN: 1294316Hom.: 489277 Cov.: 18 AF XY: 0.868 AC XY: 560294AN XY: 645254
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GnomAD4 genome ? AF: 0.891 AC: 135354AN: 151952Hom.: 60405 Cov.: 33 AF XY: 0.890 AC XY: 66080AN XY: 74276
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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:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Primary erythromelalgia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Channelopathy-associated congenital insensitivity to pain, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Paroxysmal extreme pain disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
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