2-166046984-CAAA-CA

Position:

chr2-166046984-CAAA-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001165963.4(SCN1A):c.1171-10_1171-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,612,376 control chromosomes in the GnomAD database, including 1,340 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 72 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1268 hom. )

Consequence

SCN1A
NM_001165963.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.89

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-166046984-CAA-C is Benign according to our data. Variant chr2-166046984-CAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 93628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-166046984-CAA-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0286 (4347/152212) while in subpopulation NFE AF= 0.0424 (2885/68014). AF 95% confidence interval is 0.0411. There are 72 homozygotes in gnomad4. There are 2081 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4347 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN1A	NM_001165963.4 linkuse as main transcript	c.1171-10_1171-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000674923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1A	ENST00000674923.1 linkuse as main transcript	c.1171-10_1171-9del		splice_polypyrimidine_tract_variant, intron_variant			NM_001165963.4	P4	P35498-1
SCN1A-AS1	ENST00000651574.1 linkuse as main transcript	n.487+10858_487+10859del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4349

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0280

AC:

6990

AN:

249920

Hom.:

135

AF XY:

0.0277

AC XY:

3750

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.0434

Gnomad NFE exome

AF:

0.0414

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0392

AC:

57286

AN:

1460164

Hom.:

1268

AF XY:

0.0380

AC XY:

27579

AN XY:

726536

show subpopulations

Gnomad4 AFR exome

AF:

0.00577

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00449

Gnomad4 FIN exome

AF:

0.0396

Gnomad4 NFE exome

AF:

0.0459

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0286

AC:

4347

AN:

152212

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2081

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00848

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0313

Hom.:

Bravo

AF:

0.0274

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 19, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 06, 2020	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Familial hemiplegic migraine

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Epilepsy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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