19-35030437-GGCCGCCGCCGCCGCCGCC-GGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr19-35030437-G-GGCCGCC
• rs557140301
• NM_001037.5:c.-384_-383insGCCGCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001037.5(SCN1B):​c.-384_-383insGCCGCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000976 in 182,394 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 0.0011 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00055 (0 hom.)
• 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00107 (160/149836) while in subpopulation AFR AF= 0.0033 (135/40950). AF 95% confidence interval is 0.00284. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 160 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 157 AN: 149744 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000463

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000194

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000553 AC: 18 AN: 32558 Hom.: 0 Cov.: 0 AF XY: 0.000469 AC XY: 11 AN XY: 23446

Gnomad4 AFR exome AF: 0.00472

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000621

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000565

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00107 AC: 160 AN: 149836 Hom.: 0 Cov.: 30 AF XY: 0.00101 AC XY: 74 AN XY: 73116

Gnomad4 AFR AF: 0.00330

Gnomad4 AMR AF: 0.000462

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000194

Gnomad4 OTH AF: 0.00

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;