Genetic Variant ENST00000409050.2:c.-188+14121G>A (chr2-166134926-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000409050.2(SCN1A):c.-188+14121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,932 control chromosomes in the GnomAD database, including 5,259 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. The gene SCN1A is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.26 ( 5259 hom., cov: 32)

Consequence

SCN1A
ENST00000409050.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.238

Publications

2 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

Specifications for SCN1A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409050.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN1A	NM_001202435.3	c.-142+14121G>A	intron	N/A	NP_001189364.1	P35498-1
SCN1A	NM_001353949.2	c.-50+14121G>A	intron	N/A	NP_001340878.1	P35498-2
SCN1A	NM_001353950.2	c.-142+14121G>A	intron	N/A	NP_001340879.1	P35498-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN1A	ENST00000409050.2	TSL:5	c.-188+14121G>A	intron	N/A	ENSP00000386312.1	P35498-3
SCN1A-AS1	ENST00000447809.2	TSL:1	n.260-36461C>T	intron	N/A
SCN1A	ENST00000635750.1	TSL:5	c.-50+14121G>A	intron	N/A	ENSP00000490799.1	P35498-2

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39060

AN:

151814

Hom.:

5255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.273

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

GnomAD4 genome

AF:

0.257

AC:

39086

AN:

151932

Hom.:

5259

Cov.:

AF XY:

0.257

AC XY:

19097

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.211

AC:

8735

AN:

41428

American (AMR)

AF:

0.368

AC:

5611

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1071

AN:

3468

East Asian (EAS)

AF:

0.317

AC:

1634

AN:

5156

South Asian (SAS)

AF:

0.198

AC:

952

AN:

4816

European-Finnish (FIN)

AF:

0.247

AC:

2607

AN:

10560

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17666

AN:

67936

Other (OTH)

AF:

0.275

AC:

578

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1470

2940

4410

5880

7350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.136

Hom.:

256

Bravo

AF:

0.265

Asia WGS

AF:

0.268

AC:

931

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.4

(source)

DANN

Benign

0.62

PhyloP100

-0.24

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over