chr19-35030812-C-T

Variant names:

• chr19-35030812-C-T
• rs66671189
• NM_001037.5:c.-9C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037.5(SCN1B):​c.-9C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 930,804 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: SCN1B NM_001037.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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.-9C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_001037.5	MANE Select	c.-9C>T		5_prime_UTR	Exon 1 of 6	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.-9C>T		5_prime_UTR_premature_start_codon_gain	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.-9C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.-9C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.-9C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 13934 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 930804 Hom.: 0 Cov.: 13 AF XY: 0.00000218 AC XY: 1 AN XY: 458428

African (AFR) AF: 0.00 AC: 0 AN: 17290

American (AMR) AF: 0.00 AC: 0 AN: 8198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10680

East Asian (EAS) AF: 0.00 AC: 0 AN: 13382

South Asian (SAS) AF: 0.00 AC: 0 AN: 42708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 783462

Other (OTH) AF: 0.0000293 AC: 1 AN: 34140

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.7
DANN	Benign	0.96
PhyloP100		-1.5
PromoterAI		-0.0046	Neutral

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

dbSNP: rs66671189; hg19: chr19-35521716; COSMIC: COSV52894971; COSMIC: COSV52894971;