chr19-35030595-C-T

Position:

• chr19-35030595-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001037.5(SCN1B):​c.-226C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 152,202 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (15 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 19-35030595-C-T is Benign according to our data. Variant chr19-35030595-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 675777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1093/147180) while in subpopulation AFR AF= 0.0234 (959/41000). AF 95% confidence interval is 0.0222. There are 15 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1093 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN1B	NM_001037.5	c.-226C>T		5_prime_UTR_variant	1/6	ENST00000262631.11
SCN1B	NM_199037.5	c.-226C>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1B	ENST00000262631.11	c.-226C>T		5_prime_UTR_variant	1/6	1	NM_001037.5	P1
SCN1B	ENST00000415950.5	c.-226C>T		5_prime_UTR_variant	1/3	1
SCN1B	ENST00000638536.1			upstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.00740 AC: 1089 AN: 147074 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00486

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000228

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.00933

GnomAD4 exome AF: 0.00139 AC: 7 AN: 5022 Hom.: 0 Cov.: 0 AF XY: 0.000717 AC XY: 2 AN XY: 2788

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000659

Gnomad4 OTH exome AF: 0.00340

GnomAD4 genome AF: 0.00743 AC: 1093 AN: 147180 Hom.: 15 Cov.: 31 AF XY: 0.00709 AC XY: 508 AN XY: 71694

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.00485

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000228

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.00923

Alfa AF: 0.000163 Hom.: 0

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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77001837; hg19: chr19-35521499;