rs569134158

Variant names:

• chr19-35030726-C-T
• rs569134158
• NM_001037.5:c.-95C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001037.5(SCN1B):​c.-95C>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 0.00222 in 395,560 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 31)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0560
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 19-35030726-C-T is Benign according to our data. Variant chr19-35030726-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 328830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (800/148648) while in subpopulation AFR AF = 0.0186 (766/41146). AF 95% confidence interval is 0.0175. There are 7 homozygotes in GnomAd4. There are 369 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AD,Unknown,AR gene

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.-95C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_001037.5	MANE Select	c.-95C>T		5_prime_UTR	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.-95C>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.-95C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.-95C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.-95C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 800 AN: 148540 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00153

Gnomad ASJ AF: 0.00147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00341

GnomAD4 exome AF: 0.000316 AC: 78 AN: 246912 Hom.: 0 Cov.: 4 AF XY: 0.000230 AC XY: 33 AN XY: 143746

African (AFR) AF: 0.0127 AC: 56 AN: 4402

American (AMR) AF: 0.000413 AC: 5 AN: 12096

Ashkenazi Jewish (ASJ) AF: 0.000753 AC: 6 AN: 7964

East Asian (EAS) AF: 0.00 AC: 0 AN: 7798

South Asian (SAS) AF: 0.00 AC: 0 AN: 37736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 942

European-Non Finnish (NFE) AF: 0.0000270 AC: 4 AN: 148294

Other (OTH) AF: 0.000621 AC: 7 AN: 11272

GnomAD4 genome AF: 0.00538 AC: 800 AN: 148648 Hom.: 7 Cov.: 31 AF XY: 0.00509 AC XY: 369 AN XY: 72454

African (AFR) AF: 0.0186 AC: 766 AN: 41146

American (AMR) AF: 0.00146 AC: 22 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00147 AC: 5 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66508

Other (OTH) AF: 0.00338 AC: 7 AN: 2074

Alfa AF: 0.00381 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome 5 (1)
-	-	1	Generalized epilepsy with febrile seizures plus, type 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
PhyloP100		-0.056
PromoterAI		-0.081	Neutral
Mutation Taster		=298/2	polymorphism

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: rs569134158; hg19: chr19-35521630;