chr19-35030437-GGCCGCCGCCGCC-G

Position:

• chr19-35030437-GGCCGCCGCCGCC-G

Variant summary

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

The 19-35030437-GGCCGCCGCCGCC-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 182,318 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (23 hom., cov: 30)
  • Exomes 𝑓: 0.00058 (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-GGCCGCCGCCGCC-G is Benign according to our data. Variant chr19-35030437-GGCCGCCGCCGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1198135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2315/149828) while in subpopulation NFE AF= 0.0223 (1494/67052). AF 95% confidence interval is 0.0213. There are 23 homozygotes in gnomad4. There are 1101 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2315 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: 0.0155 AC: 2316 AN: 149736 Hom.: 23 Cov.: 30

Gnomad AFR AF: 0.00397

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.0195

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.00632

GnomAD4 exome AF: 0.000585 AC: 19 AN: 32490 Hom.: 0 AF XY: 0.000641 AC XY: 15 AN XY: 23398

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: 0.00187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000526

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0155 AC: 2315 AN: 149828 Hom.: 23 Cov.: 30 AF XY: 0.0151 AC XY: 1101 AN XY: 73108

Gnomad4 AFR AF: 0.00396

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.0195

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.00625

Bravo AF: 0.0126

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;