19-35030437-GGCCGCCGCCGCCGCCGCC-GGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr19-35030437-G-GGCCGCCGCCGCC
• rs557140301
• NM_001037.5:c.-384_-383insGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001037.5(SCN1B):​c.-384_-383insGCCGCCGCCGCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 149,746 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: SCN1B NM_001037.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

SCN1B (HGNC:10586): (sodium voltage-gated channel beta subunit 1) Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.-384_-383insGCCGCCGCCGCC		upstream_gene_variant		ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.-384_-383insGCCGCCGCCGCC		upstream_gene_variant			NP_950238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11	c.-384_-383insGCCGCCGCCGCC		upstream_gene_variant		1	NM_001037.5	ENSP00000262631.3
SCN1B	ENST00000415950.5	c.-384_-383insGCCGCCGCCGCC		upstream_gene_variant		1		ENSP00000396915.2
SCN1B	ENST00000638536.1	c.-384_-383insGCCGCCGCCGCC		upstream_gene_variant		1		ENSP00000492022.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149746 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149746 Hom.: 0 Cov.: 30 AF XY: 0.0000274 AC XY: 2 AN XY: 73014

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs557140301; hg19: chr19-35521341;