rs55742440

Positions:

• chr19-35033920-T-A
• chr19-35033920-T-C
• chr19-35033920-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199037.5(SCN1B):​c.629T>A​(p.Leu210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L210P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN1B NM_199037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13669467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.448+181T>A		intron_variant		ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.629T>A	p.Leu210His	missense_variant	3/3		NP_950238.1
SCN1B	NM_001321605.2	c.349+181T>A		intron_variant			NP_001308534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11	c.448+181T>A		intron_variant		1	NM_001037.5	ENSP00000262631.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.1
DANN	Benign	0.80
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.15	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.42	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.56	N;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.096	T;.
Polyphen		0.60	P;.
Vest4		0.16
MutPred		0.23		Loss of sheet (P = 0.0025);.;
MVP		0.41
MPC		1.0
ClinPred		0.16	T
GERP RS		-1.9
gMVP		0.099

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: rs55742440; hg19: chr19-35524824;