3-38885421-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001349253.2(SCN11A):c.2950-19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,402,202 control chromosomes in the GnomAD database, including 214,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30414 hom., cov: 31)

Exomes 𝑓: 0.54 ( 184496 hom. )

Consequence

SCN11A
NM_001349253.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.819

Publications

11 publications found

Variant links:

Genes affected

SCN11A (HGNC:10583): (sodium voltage-gated channel alpha subunit 11) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is highly expressed in nociceptive neurons of dorsal root ganglia and trigeminal ganglia. It mediates brain-derived neurotrophic factor-evoked membrane depolarization and is a major effector of peripheral inflammatory pain hypersensitivity. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy type VII and familial episodic pain syndrome-3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

SCN11A Gene-Disease associations (from GenCC):

autosomal dominant hereditary sensory and autonomic neuropathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
familial episodic pain syndrome with predominantly lower limb involvement
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
hereditary sensory and autonomic neuropathy type 7
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
sodium channelopathy-related small fiber neuropathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCN11A 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=-0.91).

BP6

Variant 3-38885421-C-G is Benign according to our data. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38885421-C-G is described in CliVar as Benign. Clinvar id is 260336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN11A	NM_001349253.2 link	c.2950-19G>C		intron_variant	Intron 20 of 29	ENST00000302328.9	NP_001336182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN11A	ENST00000302328.9 link	c.2950-19G>C		intron_variant	Intron 20 of 29	5	NM_001349253.2	ENSP00000307599.3		Q9UI33-1

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93835

AN:

151938

Hom.:

30370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.587

GnomAD2 exomes

AF:

0.548

AC:

135566

AN:

247444

AF XY:

0.541

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.541

AC:

676275

AN:

1250144

Hom.:

184496

Cov.:

AF XY:

0.539

AC XY:

340679

AN XY:

632432

show subpopulations

African (AFR)

AF:

0.844

AC:

24743

AN:

29328

American (AMR)

AF:

0.483

AC:

21247

AN:

43982

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

14782

AN:

24774

East Asian (EAS)

AF:

0.552

AC:

21353

AN:

38676

South Asian (SAS)

AF:

0.498

AC:

40472

AN:

81250

European-Finnish (FIN)

AF:

0.554

AC:

29475

AN:

53188

Middle Eastern (MID)

AF:

0.531

AC:

2838

AN:

5346

European-Non Finnish (NFE)

AF:

0.535

AC:

491876

AN:

920184

Other (OTH)

AF:

0.552

AC:

29489

AN:

53416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

15186

30371

45557

60742

75928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13024

26048

39072

52096

65120

<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:

0.618

AC:

93935

AN:

152058

Hom.:

30414

Cov.:

AF XY:

0.612

AC XY:

45465

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.835

AC:

34637

AN:

41494

American (AMR)

AF:

0.498

AC:

7614

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

2100

AN:

3472

East Asian (EAS)

AF:

0.564

AC:

2913

AN:

5166

South Asian (SAS)

AF:

0.486

AC:

2339

AN:

4814

European-Finnish (FIN)

AF:

0.557

AC:

5889

AN:

10572

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.537

AC:

36488

AN:

67942

Other (OTH)

AF:

0.588

AC:

1243

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1703

3406

5108

6811

8514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.506

Hom.:

2667

Bravo

AF:

0.627

Asia WGS

AF:

0.541

AC:

1881

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial episodic pain syndrome with predominantly lower limb involvement

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary sensory and autonomic neuropathy type 7

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.91

CADD

Benign

0.75

(source)

DANN

Benign

0.47

PhyloP100

-0.82

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