rs61752574

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001349253.2(SCN11A):c.5037C>T(p.Arg1679Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,613,900 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 458 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 415 hom. )

Consequence

SCN11A
NM_001349253.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.52

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-38847033-G-A is Benign according to our data. Variant chr3-38847033-G-A is described in ClinVar as Benign. ClinVar VariationId is 474740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349253.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN11A	NM_001349253.2	MANE Select	c.5037C>T	p.Arg1679Arg	synonymous	Exon 30 of 30	NP_001336182.1
	SCN11A	NM_014139.3		c.5037C>T	p.Arg1679Arg	synonymous	Exon 26 of 26	NP_054858.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN11A	ENST00000302328.9	TSL:5 MANE Select	c.5037C>T	p.Arg1679Arg	synonymous	Exon 30 of 30	ENSP00000307599.3
SCN11A	ENST00000668754.1		c.5037C>T	p.Arg1679Arg	synonymous	Exon 33 of 33	ENSP00000499569.1
SCN11A	ENST00000456224.7	TSL:5	c.4923C>T	p.Arg1641Arg	synonymous	Exon 25 of 25	ENSP00000416757.3

Frequencies

GnomAD3 genomes

AF:

0.0418

AC:

6359

AN:

151990

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000835

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0107

AC:

2693

AN:

250782

AF XY:

0.00781

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.00723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00433

AC:

6332

AN:

1461792

Hom.:

415

Cov.:

AF XY:

0.00373

AC XY:

2714

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.150

AC:

5013

AN:

33476

American (AMR)

AF:

0.00843

AC:

377

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000429

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000256

AC:

285

AN:

1111932

Other (OTH)

AF:

0.00959

AC:

579

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

355

710

1064

1419

1774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0418

AC:

6361

AN:

152108

Hom.:

458

Cov.:

AF XY:

0.0395

AC XY:

2935

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.145

AC:

6031

AN:

41476

American (AMR)

AF:

0.0152

AC:

233

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000835

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

67996

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

265

530

795

1060

1325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0194

Hom.:

120

Bravo

AF:

0.0484

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

(source)

DANN

Benign

0.71

PhyloP100

-2.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over