Variant 19-35030556-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 964 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5 linkuse as main transcript	c.-265G>A		5_prime_UTR_variant	1/6	ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5 linkuse as main transcript	c.-265G>A		5_prime_UTR_variant	1/3		NP_950238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11 linkuse as main transcript	c.-265G>A		5_prime_UTR_variant	1/6	1	NM_001037.5	ENSP00000262631	P1	Q07699-1
SCN1B	ENST00000415950.5 linkuse as main transcript	c.-265G>A		5_prime_UTR_variant	1/3	1		ENSP00000396915		Q07699-2

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

Gnomad4 AFR exome

AF:

0.0385

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00653

AC:

964

AN:

147638

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

457

AN XY:

71942

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.00349

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000755

Gnomad4 OTH

AF:

0.00971

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.98

Splicing

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