chr19-35030437-GGCCGCCGCC-G

Position:

• chr19-35030437-GGCCGCCGCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The 19-35030437-GGCCGCCGCC-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 182,352 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (8 hom., cov: 30)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: SCN1B NM_001037.5 upstream_gene
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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-GGCCGCCGCC-G is Benign according to our data. Variant chr19-35030437-GGCCGCCGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1180393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.008 (1199/149834) while in subpopulation AFR AF= 0.0083 (340/40952). AF 95% confidence interval is 0.00757. There are 8 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1199 AD gene.

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: 0.00801 AC: 1200 AN: 149742 Hom.: 8 Cov.: 30

Gnomad AFR AF: 0.00832

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00225

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.000591

Gnomad SAS AF: 0.00693

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00574

Gnomad OTH AF: 0.00486

GnomAD4 exome AF: 0.000338 AC: 11 AN: 32518 Hom.: 0 AF XY: 0.000214 AC XY: 5 AN XY: 23416

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000310

Gnomad4 FIN exome AF: 0.00199

Gnomad4 NFE exome AF: 0.000283

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00800 AC: 1199 AN: 149834 Hom.: 8 Cov.: 30 AF XY: 0.00919 AC XY: 672 AN XY: 73112

Gnomad4 AFR AF: 0.00830

Gnomad4 AMR AF: 0.00225

Gnomad4 ASJ AF: 0.000872

Gnomad4 EAS AF: 0.000594

Gnomad4 SAS AF: 0.00673

Gnomad4 FIN AF: 0.0380

Gnomad4 NFE AF: 0.00574

Gnomad4 OTH AF: 0.00481

Bravo AF: 0.00580

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 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;