chr19-35030437-G-GGCC

Position:

• chr19-35030437-G-GGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The 19-35030437-G-GGCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 182,374 control chromosomes in the GnomAD database, including 216 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (197 hom., cov: 30)
  • Exomes 𝑓: 0.013 (19 hom.)
• Consequence: SCN1B NM_001037.5 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 19-35030437-G-GGCC is Benign according to our data. Variant chr19-35030437-G-GGCC is described in ClinVar as [Benign]. Clinvar id is 1238134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN1B	NM_001037.5			upstream_gene_variant		ENST00000262631.11
SCN1B	NM_199037.5			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1B	ENST00000262631.11			upstream_gene_variant		1	NM_001037.5	P1
SCN1B	ENST00000415950.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4801 AN: 149730 Hom.: 193 Cov.: 30

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00709

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.00600

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00486

Gnomad OTH AF: 0.0214

GnomAD4 exome AF: 0.0133 AC: 432 AN: 32552 Hom.: 19 Cov.: 0 AF XY: 0.0129 AC XY: 302 AN XY: 23440

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.00309

Gnomad4 SAS exome AF: 0.0665

Gnomad4 FIN exome AF: 0.00988

Gnomad4 NFE exome AF: 0.00496

Gnomad4 OTH exome AF: 0.0233

GnomAD4 genome AF: 0.0322 AC: 4824 AN: 149822 Hom.: 197 Cov.: 30 AF XY: 0.0333 AC XY: 2436 AN XY: 73106

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00203

Gnomad4 EAS AF: 0.00712

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.00600

Gnomad4 NFE AF: 0.00486

Gnomad4 OTH AF: 0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

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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;