rs1060499899

Positions:

• chr19-35033868-G-A
• chr19-35033868-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_199037.5(SCN1B):​c.577G>A​(p.Glu193Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: SCN1B NM_199037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10996118).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.448+129G>A		intron_variant		ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.577G>A	p.Glu193Lys	missense_variant	3/3		NP_950238.1
SCN1B	NM_001321605.2	c.349+129G>A		intron_variant			NP_001308534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11	c.448+129G>A		intron_variant		1	NM_001037.5	ENSP00000262631.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236404 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000944

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455638 Hom.: 0 Cov.: 33 AF XY: 0.00000553 AC XY: 4 AN XY: 723424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000992

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000472 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.4
DANN	Benign	0.092
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.69	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.25	N;.
REVEL	Benign	0.10
Sift	Benign	0.082	T;.
Sift4G	Benign	0.14	T;.
Polyphen		0.0030	B;.
Vest4		0.088
MutPred		0.33		Loss of sheet (P = 0.0025);.;
MVP		0.61
MPC		0.76
ClinPred		0.040	T
GERP RS		0.66
gMVP		0.29

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

Other links and lift over

dbSNP: rs1060499899; hg19: chr19-35524772;