19-35030781-C-G

Variant names:

• chr19-35030781-C-G
• rs587781150
• NM_001037.5:c.-40C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The NM_001037.5(SCN1B):​c.-40C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 867,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.967
• Publications: 0 publications found

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]

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-35030781-C-G is Benign according to our data. Variant chr19-35030781-C-G is described in ClinVar as [Benign]. Clinvar id is 139001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000738 (53/717920) while in subpopulation NFE AF = 0.0000906 (52/574062). AF 95% confidence interval is 0.0000703. There are 0 homozygotes in GnomAdExome4. There are 34 alleles in the male GnomAdExome4 subpopulation. Median coverage is 10. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.-40C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.-40C>G		5_prime_UTR_variant	Exon 1 of 3		NP_950238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11	c.-40C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3

Frequencies

GnomAD3 genomes AF: 0.0000536 AC: 8 AN: 149306 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000748

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 42268 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000738 AC: 53 AN: 717920 Hom.: 0 Cov.: 10 AF XY: 0.0000932 AC XY: 34 AN XY: 364694

African (AFR) AF: 0.00 AC: 0 AN: 13600

American (AMR) AF: 0.0000745 AC: 1 AN: 13428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11532

East Asian (EAS) AF: 0.00 AC: 0 AN: 11148

South Asian (SAS) AF: 0.00 AC: 0 AN: 46354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2022

European-Non Finnish (NFE) AF: 0.0000906 AC: 52 AN: 574062

Other (OTH) AF: 0.00 AC: 0 AN: 27016

GnomAD4 genome AF: 0.0000536 AC: 8 AN: 149306 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 4 AN XY: 72770

African (AFR) AF: 0.0000243 AC: 1 AN: 41154

American (AMR) AF: 0.000133 AC: 2 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000748 AC: 5 AN: 66846

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 14, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.40
CADD	Benign	21
DANN	Benign	0.92
PhyloP100		0.97
PromoterAI		-0.044	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs587781150; hg19: chr19-35521685;