19-35033831-C-G

Variant names:

• chr19-35033831-C-G
• rs750396627
• ENST00000415950.5:c.540C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The ENST00000415950.5(SCN1B):​c.540C>G​(p.Leu180Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L180L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN1B ENST00000415950.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.495
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-35033831-C-G is Benign according to our data. Variant chr19-35033831-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 413983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.495 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415950.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	NM_001037.5	MANE Select	c.448+92C>G		intron	N/A	NP_001028.1
	SCN1B	NM_199037.5		c.540C>G	p.Leu180Leu	synonymous	Exon 3 of 3	NP_950238.1
	SCN1B	NM_001321605.2		c.349+92C>G		intron	N/A	NP_001308534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	ENST00000415950.5	TSL:1	c.540C>G	p.Leu180Leu	synonymous	Exon 3 of 3	ENSP00000396915.2
	SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.448+92C>G		intron	N/A	ENSP00000262631.3
	SCN1B	ENST00000638536.1	TSL:1	c.448+92C>G		intron	N/A	ENSP00000492022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome 5 Benign:1

Sep 07, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.64
PhyloP100		-0.49

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: rs750396627; hg19: chr19-35524735; COSMIC: COSV99386743; COSMIC: COSV99386743;