19-35030812-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037.5(SCN1B):​c.-9C>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 0.0000037 in 1,079,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

1 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.74).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCN1BNM_001037.5 linkc.-9C>G 5_prime_UTR_variant Exon 1 of 6 ENST00000262631.11 NP_001028.1 Q07699-1
SCN1BNM_199037.5 linkc.-9C>G 5_prime_UTR_variant Exon 1 of 3 NP_950238.1 Q07699-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCN1BENST00000262631.11 linkc.-9C>G 5_prime_UTR_variant Exon 1 of 6 1 NM_001037.5 ENSP00000262631.3 Q07699-1

Frequencies

GnomAD3 genomes
AF:
0.00000671
AC:
1
AN:
149044
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000150
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000322
AC:
3
AN:
930806
Hom.:
0
Cov.:
13
AF XY:
0.00000436
AC XY:
2
AN XY:
458428
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
17290
American (AMR)
AF:
0.00
AC:
0
AN:
8198
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10680
East Asian (EAS)
AF:
0.00
AC:
0
AN:
13382
South Asian (SAS)
AF:
0.00
AC:
0
AN:
42708
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
18632
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2312
European-Non Finnish (NFE)
AF:
0.00000383
AC:
3
AN:
783464
Other (OTH)
AF:
0.00
AC:
0
AN:
34140
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000671
AC:
1
AN:
149044
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
72620
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41012
American (AMR)
AF:
0.00
AC:
0
AN:
15060
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3414
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5070
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4810
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9594
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
0.0000150
AC:
1
AN:
66820
Other (OTH)
AF:
0.00
AC:
0
AN:
2054
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
6.4
DANN
Benign
0.85
PhyloP100
-1.5
PromoterAI
0.028
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

Publications

Other links and lift over

dbSNP: rs66671189; hg19: chr19-35521716; API