19-35030795-G-C

Variant names:

• chr19-35030795-G-C
• rs1057520587
• NM_001037.5:c.-26G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001037.5(SCN1B):​c.-26G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,020,846 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-35030795-G-C is Benign according to our data. Variant chr19-35030795-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 379366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000803 (12/149424) while in subpopulation EAS AF = 0.000388 (2/5148). AF 95% confidence interval is 0.0000906. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.-26G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.-26G>C		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.-26G>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3

Frequencies

GnomAD3 genomes AF: 0.0000803 AC: 12 AN: 149424 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000598

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 27750 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: 0.00000803 AC: 7 AN: 871422 Hom.: 0 Cov.: 12 AF XY: 0.00000693 AC XY: 3 AN XY: 433110

African (AFR) AF: 0.00 AC: 0 AN: 16232

American (AMR) AF: 0.000101 AC: 1 AN: 9902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11232

East Asian (EAS) AF: 0.000318 AC: 4 AN: 12570

South Asian (SAS) AF: 0.00 AC: 0 AN: 44922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2266

European-Non Finnish (NFE) AF: 0.00000276 AC: 2 AN: 723412

Other (OTH) AF: 0.00 AC: 0 AN: 32116

GnomAD4 genome AF: 0.0000803 AC: 12 AN: 149424 Hom.: 0 Cov.: 31 AF XY: 0.0000824 AC XY: 6 AN XY: 72832

African (AFR) AF: 0.00 AC: 0 AN: 41162

American (AMR) AF: 0.000265 AC: 4 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000208 AC: 2 AN: 9604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000598 AC: 4 AN: 66910

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 21, 2015

GeneDx

Significance: Likely 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	-0.50
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-1.4
PromoterAI		0.078	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1057520587; hg19: chr19-35521699;