2-165990220-A-G

Position:

chr2-165990220-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001165963.4(SCN1A):c.*1025T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.137 in 152,572 control chromosomes in the GnomAD database, including 1,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1820 hom., cov: 32)

Exomes 𝑓: 0.22 ( 11 hom. )

Consequence

SCN1A
NM_001165963.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.89

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:

LOC102724058 (HGNC:):

LOC102724058 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-165990220-A-G is Benign according to our data. Variant chr2-165990220-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 331869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001165963.4 linkuse as main transcript	c.*1025T>C		3_prime_UTR_variant	29/29	ENST00000674923.1	NP_001159435.1
LOC102724058	NR_110598.1 linkuse as main transcript	n.176-25393A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1 linkuse as main transcript	c.*1025T>C		3_prime_UTR_variant	29/29		NM_001165963.4	ENSP00000501589	P4	P35498-1
SCN1A-AS1	ENST00000651574.1 linkuse as main transcript	n.193-25393A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20843

AN:

152018

Hom.:

1818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0674

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.222

AC:

AN:

436

Hom.:

Cov.:

AF XY:

0.242

AC XY:

AN XY:

264

show subpopulations

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.137

AC:

20865

AN:

152136

Hom.:

1820

Cov.:

AF XY:

0.144

AC XY:

10681

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.0596

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.140

Hom.:

2263

Bravo

AF:

0.139

Asia WGS

AF:

0.223

AC:

774

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Migraine, familial hemiplegic, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Generalized epilepsy with febrile seizures plus, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.88

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

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