rs150633320

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001365536.1(SCN9A):c.4399-10_4399-7delGTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,507,680 control chromosomes in the GnomAD database, including 573,967 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60110 hom., cov: 0)

Exomes 𝑓: 0.87 ( 513857 hom. )

Consequence

SCN9A
NM_001365536.1 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 0.886

Publications

5 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 -16 ACMG points.

BP6

Variant 2-166204470-GAAAC-G is Benign according to our data. Variant chr2-166204470-GAAAC-G is described in ClinVar as Benign. ClinVar VariationId is 167657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1 link	c.4399-10_4399-7delGTTT		splice_region_variant, intron_variant	Intron 24 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SCN9A	ENST00000642356.2 link	c.4399-10_4399-7delGTTT	splice_region_variant, intron_variant	Intron 24 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11 link	c.4399-10_4399-7delGTTT	splice_region_variant, intron_variant	Intron 24 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5 link	c.4366-10_4366-7delGTTT	splice_region_variant, intron_variant	Intron 24 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1 link	c.4366-10_4366-7delGTTT	splice_region_variant, intron_variant	Intron 24 of 26			ENSP00000495983.1

Frequencies

GnomAD3 genomes

AF:

0.890

AC:

134739

AN:

151410

Hom.:

60067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.886

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.937

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.879

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.881

AC:

195432

AN:

221844

AF XY:

0.877

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.903

Gnomad ASJ exome

AF:

0.911

Gnomad EAS exome

AF:

0.938

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.875

GnomAD4 exome

AF:

0.869

AC:

1178638

AN:

1356152

Hom.:

513857

AF XY:

0.868

AC XY:

586267

AN XY:

675432

show subpopulations

African (AFR)

AF:

0.937

AC:

28230

AN:

30118

American (AMR)

AF:

0.899

AC:

31883

AN:

35464

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

21670

AN:

23894

East Asian (EAS)

AF:

0.940

AC:

36477

AN:

38810

South Asian (SAS)

AF:

0.836

AC:

61822

AN:

73968

European-Finnish (FIN)

AF:

0.894

AC:

46577

AN:

52102

Middle Eastern (MID)

AF:

0.867

AC:

3325

AN:

3834

European-Non Finnish (NFE)

AF:

0.863

AC:

899374

AN:

1041828

Other (OTH)

AF:

0.878

AC:

49280

AN:

56134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7104

14208

21311

28415

35519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19786

39572

59358

79144

98930

<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:

0.890

AC:

134838

AN:

151528

Hom.:

60110

Cov.:

AF XY:

0.889

AC XY:

65760

AN XY:

74008

show subpopulations

African (AFR)

AF:

0.937

AC:

38809

AN:

41410

American (AMR)

AF:

0.886

AC:

13463

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3154

AN:

3466

East Asian (EAS)

AF:

0.937

AC:

4839

AN:

5162

South Asian (SAS)

AF:

0.826

AC:

3970

AN:

4804

European-Finnish (FIN)

AF:

0.886

AC:

9271

AN:

10464

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.863

AC:

58428

AN:

67716

Other (OTH)

AF:

0.883

AC:

1857

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

747

1495

2242

2990

3737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.884

Hom.:

10776

Bravo

AF:

0.895

Asia WGS

AF:

0.878

AC:

3027

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 27, 2014

Eurofins Ntd Llc (ga)

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 89% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 83. Only high quality variants are reported. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

May 06, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 17470132, 23129781) -

Paroxysmal extreme pain disorder

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary erythromelalgia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inherited Erythromelalgia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

- -

Congenital Indifference to Pain

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Small fiber neuropathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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