dbSNP rs1057520587: SCN1B:c.-26G>A (chr19-35030795-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037.5(SCN1B):c.-26G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,020,846 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: 0.0000034 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

Publications

0 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]

SCN1B links:

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

HPN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.-26G>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.-26G>A		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
SCN1B	ENST00000262631.11 link	c.-26G>A		5_prime_UTR_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

871422

Hom.:

Cov.:

AF XY:

0.00000231

AC XY:

AN XY:

433110

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

16232

American (AMR)

AF:

0.00

AC:

AN:

9902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11232

East Asian (EAS)

AF:

0.00

AC:

AN:

12570

South Asian (SAS)

AF:

0.0000223

AC:

AN:

44922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2266

European-Non Finnish (NFE)

AF:

0.00000138

AC:

AN:

723412

Other (OTH)

AF:

0.0000311

AC:

AN:

32116

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.004005), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41162

American (AMR)

AF:

0.0000663

AC:

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66910

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

-1.4

PromoterAI

0.011

Neutral

(source)

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

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rs1057520587

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over