2-166039633-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4 link	c.2416-37A>C		intron_variant	Intron 16 of 28	ENST00000674923.1	NP_001159435.1	P35498-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN1A	ENST00000674923.1 link	c.2416-37A>C	intron_variant	Intron 16 of 28		NM_001165963.4	ENSP00000501589.1	P35498-1
SCN1A	ENST00000303395.9 link	c.2416-37A>C	intron_variant	Intron 15 of 27	5		ENSP00000303540.4	P35498-1
SCN1A	ENST00000375405.7 link	c.2383-37A>C	intron_variant	Intron 13 of 25	5		ENSP00000364554.3	P35498-2
SCN1A	ENST00000409050.1 link	c.2332-37A>C	intron_variant	Intron 13 of 25	5		ENSP00000386312.1	P35498-3

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

GnomAD3 exomes

AF:

0.727

AC:

178504

AN:

245524

Hom.:

65691

AF XY:

0.717

AC XY:

95484

AN XY:

133248

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 SAS exome

AF:

0.687

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

Gnomad4 AFR exome

AF:

0.828

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.895

Gnomad4 SAS exome

AF:

0.684

Gnomad4 FIN exome

AF:

0.749

Gnomad4 NFE exome

AF:

0.693

Gnomad4 OTH exome

AF:

0.697

GnomAD4 genome

AF:

0.738

AC:

112167

AN:

152064

Hom.:

41772

Cov.:

AF XY:

0.741

AC XY:

55090

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.823

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.709

Gnomad4 FIN

AF:

0.756

Gnomad4 NFE

AF:

0.682

Gnomad4 OTH

AF:

0.682

Alfa

AF:

0.694

Hom.:

7625

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over