19-35033954-C-T

Variant names:

• chr19-35033954-C-T
• rs1015574605
• ENST00000415950.5:c.663C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_199037.5(SCN1B):​c.663C>T​(p.Val221Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V221V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SCN1B NM_199037.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.033 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199037.5. 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.448+215C>T		intron	N/A	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.663C>T	p.Val221Val	synonymous	Exon 3 of 3	NP_950238.1	Q07699-2
	SCN1B	NM_001321605.2		c.349+215C>T		intron	N/A	NP_001308534.1	A0A1W2PR05

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	ENST00000415950.5	TSL:1	c.663C>T	p.Val221Val	synonymous	Exon 3 of 3	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.448+215C>T		intron	N/A	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000638536.1	TSL:1	c.448+215C>T		intron	N/A	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400976 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 691322

African (AFR) AF: 0.00 AC: 0 AN: 31636

American (AMR) AF: 0.00 AC: 0 AN: 35784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35776

South Asian (SAS) AF: 0.00 AC: 0 AN: 79752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079652

Other (OTH) AF: 0.00 AC: 0 AN: 58094

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs1015574605; hg19: chr19-35524858;