rs919198

Variant names:

• chr2-165994670-C-T
• rs919198
• NM_001165963.4:c.4582-254G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001165963.4(SCN1A):​c.4582-254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 151,748 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.023 (183 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 1 publications found

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-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

LOC102724058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-165994670-C-T is Benign according to our data. Variant chr2-165994670-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1207293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.4582-254G>A		intron_variant	Intron 27 of 28	ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.4582-254G>A		intron_variant	Intron 27 of 28		NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.4582-254G>A		intron_variant	Intron 26 of 27	5		ENSP00000303540.4
SCN1A	ENST00000375405.7	c.4549-254G>A		intron_variant	Intron 24 of 25	5		ENSP00000364554.3
SCN1A	ENST00000409050.2	c.4498-254G>A		intron_variant	Intron 26 of 27	5		ENSP00000386312.1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3440 AN: 151630 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.00397

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.00706

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.0207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0227 AC: 3448 AN: 151748 Hom.: 183 Cov.: 32 AF XY: 0.0254 AC XY: 1885 AN XY: 74154

African (AFR) AF: 0.00396 AC: 164 AN: 41452

American (AMR) AF: 0.128 AC: 1942 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3466

East Asian (EAS) AF: 0.0933 AC: 478 AN: 5124

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4814

European-Finnish (FIN) AF: 0.0252 AC: 267 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00701 AC: 475 AN: 67794

Other (OTH) AF: 0.0200 AC: 42 AN: 2104

Alfa AF: 0.0135 Hom.: 10

Bravo AF: 0.0314

Asia WGS AF: 0.0430 AC: 149 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Likely 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	-0.88
CADD	Benign	0.83
DANN	Benign	0.14
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs919198; hg19: chr2-166851180;