Variant rs490317 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001165963.4(SCN1A):c.2416-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,341,646 control chromosomes in the GnomAD database, including 45,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3867 hom., cov: 32)

Exomes 𝑓: 0.26 ( 41569 hom. )

Consequence

SCN1A
NM_001165963.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.92

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-166039668-C-T is Benign according to our data. Variant chr2-166039668-C-T is described in ClinVar as [Benign]. Clinvar id is 3256826.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001165963.4 linkuse as main transcript	c.2416-72G>A		intron_variant		ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1 linkuse as main transcript	c.2416-72G>A		intron_variant			NM_001165963.4	ENSP00000501589	P4	P35498-1
SCN1A-AS1	ENST00000651574.1 linkuse as main transcript	n.487+3538C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32034

AN:

151944

Hom.:

3870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.0934

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.259

AC:

308468

AN:

1189586

Hom.:

41569

AF XY:

0.261

AC XY:

157022

AN XY:

602536

show subpopulations

Gnomad4 AFR exome

AF:

0.0882

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.0853

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.211

AC:

32028

AN:

152060

Hom.:

3867

Cov.:

AF XY:

0.206

AC XY:

15299

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0931

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.0934

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.244

Hom.:

632

Bravo

AF:

0.210

Asia WGS

AF:

0.151

AC:

527

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.4

DANN

Benign

0.68

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