2-166039633-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001165963.4(SCN1A):c.2416-37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,561,032 control chromosomes in the GnomAD database, including 393,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 41772 hom., cov: 31)

Exomes 𝑓: 0.70 ( 351405 hom. )

Consequence

SCN1A
NM_001165963.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.192

Publications

14 publications found

Variant links:

Genes affected

SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]

SCN1A 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-166039633-T-G is Benign according to our data. Variant chr2-166039633-T-G is described in ClinVar as Benign. ClinVar VariationId is 3255232.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SCN1A	NM_001165963.4	MANE Select	c.2416-37A>C	intron	N/A	NP_001159435.1
SCN1A	NM_001202435.3		c.2416-37A>C	intron	N/A	NP_001189364.1
SCN1A	NM_001353948.2		c.2416-37A>C	intron	N/A	NP_001340877.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SCN1A	ENST00000674923.1	MANE Select	c.2416-37A>C	intron	N/A	ENSP00000501589.1
SCN1A	ENST00000303395.9	TSL:5	c.2416-37A>C	intron	N/A	ENSP00000303540.4
SCN1A	ENST00000375405.7	TSL:5	c.2383-37A>C	intron	N/A	ENSP00000364554.3

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112063

AN:

151948

Hom.:

41728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.645

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.680

GnomAD2 exomes

AF:

0.727

AC:

178504

AN:

245524

AF XY:

0.717

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.677

GnomAD4 exome

AF:

0.704

AC:

992158

AN:

1408968

Hom.:

351405

Cov.:

AF XY:

0.701

AC XY:

493261

AN XY:

704152

show subpopulations

African (AFR)

AF:

0.828

AC:

26840

AN:

32406

American (AMR)

AF:

0.803

AC:

35757

AN:

44534

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

15542

AN:

25824

East Asian (EAS)

AF:

0.895

AC:

35195

AN:

39312

South Asian (SAS)

AF:

0.684

AC:

57985

AN:

84796

European-Finnish (FIN)

AF:

0.749

AC:

39884

AN:

53282

Middle Eastern (MID)

AF:

0.513

AC:

2876

AN:

5604

European-Non Finnish (NFE)

AF:

0.693

AC:

737296

AN:

1064660

Other (OTH)

AF:

0.697

AC:

40783

AN:

58550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

14396

28793

43189

57586

71982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18626

37252

55878

74504

93130

<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:

0.738

AC:

112167

AN:

152064

Hom.:

41772

Cov.:

AF XY:

0.741

AC XY:

55090

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.823

AC:

34153

AN:

41476

American (AMR)

AF:

0.742

AC:

11343

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2089

AN:

3468

East Asian (EAS)

AF:

0.891

AC:

4610

AN:

5176

South Asian (SAS)

AF:

0.709

AC:

3418

AN:

4822

European-Finnish (FIN)

AF:

0.756

AC:

7991

AN:

10566

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.682

AC:

46384

AN:

67964

Other (OTH)

AF:

0.682

AC:

1440

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.697

Hom.:

13071

Bravo

AF:

0.741

Asia WGS

AF:

0.790

AC:

2746

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

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 87% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 81. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.19

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over