19-35030794-G-T

Variant names:

• chr19-35030794-G-T
• rs758958222
• NM_001037.5:c.-27G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001037.5(SCN1B):​c.-27G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 861,992 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.43
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-35030794-G-T is Benign according to our data. Variant chr19-35030794-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 190851.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	NM_001037.5	MANE Select	c.-27G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_001037.5	MANE Select	c.-27G>T		5_prime_UTR	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.-27G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_950238.1	Q07699-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.-27G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.-27G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.-27G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 861992 Hom.: 0 Cov.: 12 AF XY: 0.00000233 AC XY: 1 AN XY: 428718

African (AFR) AF: 0.00 AC: 0 AN: 16056

American (AMR) AF: 0.00 AC: 0 AN: 9846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11146

East Asian (EAS) AF: 0.00 AC: 0 AN: 12376

South Asian (SAS) AF: 0.00 AC: 0 AN: 44662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2256

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 715248

Other (OTH) AF: 0.00 AC: 0 AN: 31778

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		2.4
PromoterAI		-0.076	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: rs758958222; hg19: chr19-35521698;