Genetic Variant SCN1B:c.-265G>A (chr19-35030556-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001037.5(SCN1B):c.-265G>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 0.00645 in 149,660 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00099 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-35030556-G-A is Benign according to our data. Variant chr19-35030556-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190623.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00653 (964/147638) while in subpopulation AFR AF = 0.0216 (885/41036). AF 95% confidence interval is 0.0204. There are 10 homozygotes in GnomAd4. There are 457 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AD,Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.-265G>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.-265G>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.-265G>A		5_prime_UTR_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

966

AN:

147532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00350

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000755

Gnomad OTH

AF:

0.00981

GnomAD4 exome

AF:

0.000989

AC:

AN:

2022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1102

show subpopulations

African (AFR)

AF:

0.0385

AC:

AN:

American (AMR)

AF:

0.0200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

854

Other (OTH)

AF:

0.00

AC:

AN:

100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00653

AC:

964

AN:

147638

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

457

AN XY:

71942

show subpopulations

African (AFR)

AF:

0.0216

AC:

885

AN:

41036

American (AMR)

AF:

0.00349

AC:

AN:

14888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

66188

Other (OTH)

AF:

0.00971

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00513

Hom.:

Asia WGS

AF:

0.000986

AC:

AN:

3054

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.5

PromoterAI

-0.0080

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr19-35030556-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over