chr2-166226609-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001365536.1(SCN9A):c.4356C>T(p.Phe1452Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.000444 in 1,585,076 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 3 hom. )
Consequence
SCN9A
NM_001365536.1 synonymous
NM_001365536.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.87
Publications
0 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 2-166226609-G-A is Benign according to our data. Variant chr2-166226609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 195815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00243 (370/152054) while in subpopulation AFR AF = 0.00851 (353/41498). AF 95% confidence interval is 0.00778. There are 3 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 3 AD,SD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.4356C>T | p.Phe1452Phe | synonymous_variant | Exon 24 of 27 | ENST00000642356.2 | NP_001352465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.4356C>T | p.Phe1452Phe | synonymous_variant | Exon 24 of 27 | NM_001365536.1 | ENSP00000495601.1 | |||
SCN9A | ENST00000303354.11 | c.4356C>T | p.Phe1452Phe | synonymous_variant | Exon 24 of 27 | 5 | ENSP00000304748.7 | |||
SCN9A | ENST00000409672.5 | c.4323C>T | p.Phe1441Phe | synonymous_variant | Exon 24 of 27 | 5 | ENSP00000386306.1 | |||
SCN9A | ENST00000645907.1 | c.4323C>T | p.Phe1441Phe | synonymous_variant | Exon 24 of 27 | ENSP00000495983.1 |
Frequencies
GnomAD3 genomes AF: 0.00244 AC: 370AN: 151936Hom.: 3 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
370
AN:
151936
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000564 AC: 133AN: 235874 AF XY: 0.000376 show subpopulations
GnomAD2 exomes
AF:
AC:
133
AN:
235874
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000233 AC: 334AN: 1433022Hom.: 3 Cov.: 27 AF XY: 0.000186 AC XY: 132AN XY: 711290 show subpopulations
GnomAD4 exome
AF:
AC:
334
AN:
1433022
Hom.:
Cov.:
27
AF XY:
AC XY:
132
AN XY:
711290
show subpopulations
African (AFR)
AF:
AC:
257
AN:
32798
American (AMR)
AF:
AC:
22
AN:
42846
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25502
East Asian (EAS)
AF:
AC:
0
AN:
38974
South Asian (SAS)
AF:
AC:
5
AN:
79044
European-Finnish (FIN)
AF:
AC:
0
AN:
52528
Middle Eastern (MID)
AF:
AC:
2
AN:
5698
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1096378
Other (OTH)
AF:
AC:
38
AN:
59254
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.437
Heterozygous variant carriers
0
14
28
43
57
71
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.00243 AC: 370AN: 152054Hom.: 3 Cov.: 32 AF XY: 0.00225 AC XY: 167AN XY: 74328 show subpopulations
GnomAD4 genome
AF:
AC:
370
AN:
152054
Hom.:
Cov.:
32
AF XY:
AC XY:
167
AN XY:
74328
show subpopulations
African (AFR)
AF:
AC:
353
AN:
41498
American (AMR)
AF:
AC:
12
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10588
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67918
Other (OTH)
AF:
AC:
5
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
18
36
54
72
90
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3470
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
SCN9A: BP4, BP7, BS2 -
Nov 01, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Benign:1
Apr 02, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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