chr2-166203939-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0760

Publications

10 publications found

Variant links:

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]

SCN9A links:

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

SCN1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 258888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1 link	c.4774+16T>A		intron_variant	Intron 26 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN9A	ENST00000642356.2 link	c.4774+16T>A	intron_variant	Intron 26 of 26		NM_001365536.1	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11 link	c.4774+16T>A	intron_variant	Intron 26 of 26	5		ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5 link	c.4741+16T>A	intron_variant	Intron 26 of 26	5		ENSP00000386306.1	Q15858-3
SCN9A	ENST00000645907.1 link	c.4741+16T>A	intron_variant	Intron 26 of 26			ENSP00000495983.1	Q15858-4

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135255

AN:

151834

Hom.:

60362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.886

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.951

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.883

AC:

158939

AN:

179950

AF XY:

0.880

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.906

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.953

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.863

Gnomad OTH exome

AF:

0.875

GnomAD4 exome

AF:

0.869

AC:

1124794

AN:

1294316

Hom.:

489277

Cov.:

AF XY:

0.868

AC XY:

560294

AN XY:

645254

show subpopulations

African (AFR)

AF:

0.937

AC:

26995

AN:

28816

American (AMR)

AF:

0.902

AC:

31594

AN:

35044

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

21483

AN:

23680

East Asian (EAS)

AF:

0.949

AC:

35065

AN:

36962

South Asian (SAS)

AF:

0.839

AC:

62674

AN:

74736

European-Finnish (FIN)

AF:

0.895

AC:

44807

AN:

50082

Middle Eastern (MID)

AF:

0.873

AC:

4638

AN:

5314

European-Non Finnish (NFE)

AF:

0.863

AC:

849943

AN:

985420

Other (OTH)

AF:

0.877

AC:

47595

AN:

54262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6418

12836

19255

25673

32091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18500

37000

55500

74000

92500

<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:

0.891

AC:

135354

AN:

151952

Hom.:

60405

Cov.:

AF XY:

0.890

AC XY:

66080

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.937

AC:

38957

AN:

41558

American (AMR)

AF:

0.886

AC:

13508

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3156

AN:

3468

East Asian (EAS)

AF:

0.950

AC:

4923

AN:

5180

South Asian (SAS)

AF:

0.830

AC:

3994

AN:

4814

European-Finnish (FIN)

AF:

0.888

AC:

9403

AN:

10594

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58503

AN:

67782

Other (OTH)

AF:

0.882

AC:

1860

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

757

1514

2271

3028

3785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.886

Hom.:

10973

Bravo

AF:

0.896

Asia WGS

AF:

0.886

AC:

3078

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 88. Only high quality variants are reported. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary erythromelalgia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Channelopathy-associated congenital insensitivity to pain, autosomal recessive

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Paroxysmal extreme pain disorder

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.3

(source)

DANN

Benign

0.80

PhyloP100

-0.076

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over