rs55742440

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199037.5(SCN1B):c.629T>C(p.Leu210Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,567,610 control chromosomes in the GnomAD database, including 110,048 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13648 hom., cov: 32)

Exomes 𝑓: 0.37 ( 96400 hom. )

Consequence

SCN1B
NM_199037.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0130

Publications

41 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.393751E-5).

BP6

Variant 19-35033920-T-C is Benign according to our data. Variant chr19-35033920-T-C is described in ClinVar as Benign. ClinVar VariationId is 138998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCN1B	NM_001037.5	MANE Select	c.448+181T>C		intron	N/A	NP_001028.1	Q07699-1
SCN1B	NM_199037.5		c.629T>C	p.Leu210Pro	missense	Exon 3 of 3	NP_950238.1	Q07699-2
SCN1B	NM_001321605.2		c.349+181T>C		intron	N/A	NP_001308534.1	A0A1W2PR05

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCN1B	ENST00000415950.5	TSL:1	c.629T>C	p.Leu210Pro	missense	Exon 3 of 3	ENSP00000396915.2	Q07699-2
SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.448+181T>C		intron	N/A	ENSP00000262631.3	Q07699-1
SCN1B	ENST00000638536.1	TSL:1	c.448+181T>C		intron	N/A	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63377

AN:

151816

Hom.:

13627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.368

AC:

65107

AN:

176726

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.365

AC:

517037

AN:

1415674

Hom.:

96400

Cov.:

AF XY:

0.364

AC XY:

254721

AN XY:

700160

show subpopulations

African (AFR)

AF:

0.533

AC:

17159

AN:

32208

American (AMR)

AF:

0.323

AC:

11902

AN:

36826

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

12635

AN:

25344

East Asian (EAS)

AF:

0.265

AC:

9733

AN:

36706

South Asian (SAS)

AF:

0.293

AC:

23966

AN:

81744

European-Finnish (FIN)

AF:

0.395

AC:

19935

AN:

50460

Middle Eastern (MID)

AF:

0.510

AC:

2911

AN:

5708

European-Non Finnish (NFE)

AF:

0.364

AC:

395992

AN:

1087988

Other (OTH)

AF:

0.389

AC:

22804

AN:

58690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19394

38787

58181

77574

96968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12514

25028

37542

50056

62570

<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:

0.418

AC:

63438

AN:

151936

Hom.:

13648

Cov.:

AF XY:

0.417

AC XY:

30958

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.523

AC:

21671

AN:

41438

American (AMR)

AF:

0.386

AC:

5892

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

1755

AN:

3466

East Asian (EAS)

AF:

0.258

AC:

1323

AN:

5134

South Asian (SAS)

AF:

0.299

AC:

1438

AN:

4810

European-Finnish (FIN)

AF:

0.404

AC:

4271

AN:

10574

Middle Eastern (MID)

AF:

0.514

AC:

150

AN:

292

European-Non Finnish (NFE)

AF:

0.377

AC:

25629

AN:

67926

Other (OTH)

AF:

0.446

AC:

942

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1888

3776

5664

7552

9440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.390

Hom.:

22232

Bravo

AF:

0.421

TwinsUK

AF:

0.360

AC:

1334

ALSPAC

AF:

0.373

AC:

1438

ESP6500AA

AF:

0.509

AC:

1290

ESP6500EA

AF:

0.372

AC:

1675

ExAC

AF:

0.327

AC:

35882

Asia WGS

AF:

0.299

AC:

1039

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Brugada syndrome 5 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.5

(source)

DANN

Benign

0.60

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00025

LIST_S2

Benign

0.14

MetaRNN

Benign

0.000084

MetaSVM

Benign

-0.98

PhyloP100

-0.013

PrimateAI

Benign

0.23

PROVEAN

Benign

1.8

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Benign

0.062

Polyphen

0.0

Vest4

0.024

MPC

1.1

ClinPred

0.0078

GERP RS

-1.9

gMVP

0.11

Mutation Taster

=99/1

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over