2-166134926-C-T

Variant names:

• chr2-166134926-C-T
• rs16851603
• ENST00000409050.2:c.-188+14121G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001202435.3(SCN1A):​c.-142+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.

• Frequency: Genomes: 𝑓 0.26 (5259 hom., cov: 32)
• Consequence: SCN1A NM_001202435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 2 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)

ACMG classification

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: NM_001202435.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

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.: 32 AF XY: 0.257 AC XY: 19097 AN XY: 74276

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: 66 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17666 AN: 67936

Other (OTH) AF: 0.275 AC: 578 AN: 2104

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
DANN	Benign	0.62
PhyloP100		-0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16851603; hg19: chr2-166991436;