NM_001037.5:c.8G>T

Variant names:

• chr19-35030828-G-T
• NM_001037.5:c.8G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001037.5(SCN1B):​c.8G>T​(p.Arg3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 938,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SCN1B NM_001037.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.0240
• Publications: 0 publications found

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]

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2290327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	NM_001037.5	MANE Select	c.8G>T	p.Arg3Met	missense	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.8G>T	p.Arg3Met	missense	Exon 1 of 3	NP_950238.1	Q07699-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.8G>T	p.Arg3Met	missense	Exon 1 of 6	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.8G>T	p.Arg3Met	missense	Exon 1 of 3	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.8G>T	p.Arg3Met	missense	Exon 1 of 5	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000746 AC: 7 AN: 938412 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 457982

African (AFR) AF: 0.00 AC: 0 AN: 17450

American (AMR) AF: 0.00 AC: 0 AN: 6966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10160

East Asian (EAS) AF: 0.00 AC: 0 AN: 13662

South Asian (SAS) AF: 0.00 AC: 0 AN: 39656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2300

European-Non Finnish (NFE) AF: 0.00000880 AC: 7 AN: 795540

Other (OTH) AF: 0.00 AC: 0 AN: 34434

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Brugada syndrome 5 (1)
-	1	-	Cardiovascular phenotype (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	0.0	N
PhyloP100		0.024
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.46	N
REVEL	Uncertain	0.30
Sift	Benign	0.11	T
Sift4G	Benign	0.10	T
Polyphen		0.70	P
Vest4		0.21
MutPred		0.35		Loss of methylation at R3 (P = 0.0101)
MVP		0.84
MPC		0.75
ClinPred		0.067	T
GERP RS		0.0044
PromoterAI		-0.19	Neutral
Varity_R		0.054
gMVP		0.52
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr19-35521732;