Variant chr19-35030733-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001037.5(SCN1B):c.-88A>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 0.000354 in 386,554 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000353 (52/147264) while in subpopulation NFE AF= 0.000696 (46/66080). AF 95% confidence interval is 0.000536. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN1B	NM_001037.5 linkuse as main transcript	c.-88A>C		5_prime_UTR_variant	1/6	ENST00000262631.11
SCN1B	NM_199037.5 linkuse as main transcript	c.-88A>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1B	ENST00000262631.11 linkuse as main transcript	c.-88A>C	5_prime_UTR_variant	1/6	1	NM_001037.5	P1	Q07699-1
SCN1B	ENST00000415950.5 linkuse as main transcript	c.-88A>C	5_prime_UTR_variant	1/3	1			Q07699-2
SCN1B	ENST00000638536.1 linkuse as main transcript	c.-88A>C	5_prime_UTR_variant	1/5	1		P1	Q07699-1
SCN1B	ENST00000595652.5 linkuse as main transcript	c.-88A>C	5_prime_UTR_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

147264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000696

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000355

AC:

AN:

239290

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

AN XY:

139578

show subpopulations

Gnomad4 AFR exome

AF:

0.000236

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.000396

Gnomad4 NFE exome

AF:

0.000484

Gnomad4 OTH exome

AF:

0.000582

GnomAD4 genome

AF:

0.000353

AC:

AN:

147264

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

AN XY:

71744

show subpopulations

Gnomad4 AFR

AF:

0.0000983

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000108

Gnomad4 NFE

AF:

0.000696

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brugada syndrome 5

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Generalized epilepsy with febrile seizures plus, type 1;C2748541:Brugada syndrome 5;C3809311:Atrial fibrillation, familial, 13;C4479236:Developmental and epileptic encephalopathy, 52

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 28, 2021

- -

Generalized epilepsy with febrile seizures plus, type 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over