dbSNP rs10188577: SCN1A:c.265-699A>G (chr2-166059387-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001165963.4(SCN1A):c.265-699A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,086 control chromosomes in the GnomAD database, including 5,858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5858 hom., cov: 31)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

SCN1A
NM_001165963.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.508

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4 link	c.265-699A>G		intron_variant	Intron 4 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.265-699A>G	intron_variant	Intron 4 of 28		NM_001165963.4	ENSP00000501589.1	P35498-1
SCN1A	ENST00000303395.9 link	c.265-699A>G	intron_variant	Intron 3 of 27	5		ENSP00000303540.4	P35498-1
SCN1A	ENST00000375405.7 link	c.265-699A>G	intron_variant	Intron 1 of 25	5		ENSP00000364554.3	P35498-2
SCN1A	ENST00000409050.2 link	c.265-699A>G	intron_variant	Intron 3 of 27	5		ENSP00000386312.1	P35498-3

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39622

AN:

151958

Hom.:

5858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.100

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.261

AC:

39625

AN:

152076

Hom.:

5858

Cov.:

AF XY:

0.258

AC XY:

19174

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.123

AC:

5116

AN:

41518

American (AMR)

AF:

0.234

AC:

3577

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1334

AN:

3466

East Asian (EAS)

AF:

0.193

AC:

999

AN:

5170

South Asian (SAS)

AF:

0.272

AC:

1311

AN:

4818

European-Finnish (FIN)

AF:

0.298

AC:

3157

AN:

10580

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23099

AN:

67940

Other (OTH)

AF:

0.298

AC:

628

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1446

2891

4337

5782

7228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.311

Hom.:

19474

Bravo

AF:

0.248

Asia WGS

AF:

0.244

AC:

847

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.4

(source)

DANN

Benign

0.67

PhyloP100

0.51

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over