rs754815235

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The ENST00000415950.5(SCN1B):c.793C>T(p.Arg265Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,551,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R265Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SCN1B
ENST00000415950.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.223

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04147473).

BP6

Variant 19-35034084-C-T is Benign according to our data. Variant chr19-35034084-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 190866.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000184 (28/152124) while in subpopulation AFR AF = 0.000652 (27/41420). AF 95% confidence interval is 0.00046. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415950.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN1B	NM_001037.5	MANE Select	c.448+345C>T		intron	N/A	NP_001028.1
SCN1B	NM_199037.5		c.793C>T	p.Arg265Trp	missense	Exon 3 of 3	NP_950238.1
SCN1B	NM_001321605.2		c.349+345C>T		intron	N/A	NP_001308534.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN1B	ENST00000415950.5	TSL:1	c.793C>T	p.Arg265Trp	missense	Exon 3 of 3	ENSP00000396915.2
SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.448+345C>T		intron	N/A	ENSP00000262631.3
SCN1B	ENST00000638536.1	TSL:1	c.448+345C>T		intron	N/A	ENSP00000492022.1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000585

AC:

AN:

153834

AF XY:

0.0000491

show subpopulations

Gnomad AFR exome

AF:

0.000630

Gnomad AMR exome

AF:

0.0000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000386

AC:

AN:

1399326

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

690188

show subpopulations

African (AFR)

AF:

0.000886

AC:

AN:

31598

American (AMR)

AF:

0.0000560

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000252

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1078890

Other (OTH)

AF:

0.000155

AC:

AN:

58008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000184

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.000652

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000328

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000314

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brugada syndrome 5 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.3

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.42

M_CAP

Benign

0.059

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.68

PhyloP100

0.22

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.23

REVEL

Benign

0.083

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.16

MVP

0.44

MPC

1.6

ClinPred

0.12

GERP RS

-0.064

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over