ENST00000530277:c.*178G>C

Variant names:

• chr11-123633965-C-G
• rs1148111
• ENST00000530277:c.*178G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000530277(SCN3B):​c.*178G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 640,256 control chromosomes in the GnomAD database, including 127,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35856 hom., cov: 32)
  • Exomes 𝑓: 0.60 (92053 hom.)
• Consequence: SCN3B ENST00000530277 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.139

Genes affected

SCN3B (HGNC:20665): (sodium voltage-gated channel beta subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-123633965-C-G is Benign according to our data. Variant chr11-123633965-C-G is described in ClinVar as [Benign]. Clinvar id is 671838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3B	NM_001040151.2	c.*22+156G>C		intron_variant	Intron 6 of 6	ENST00000299333.8	NP_001035241.1
SCN3B	NM_018400.4	c.*22+156G>C		intron_variant	Intron 5 of 5		NP_060870.1
SCN3B	XM_011542897.3	c.*22+156G>C		intron_variant	Intron 6 of 6		XP_011541199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8	c.*22+156G>C		intron_variant	Intron 6 of 6	1	NM_001040151.2	ENSP00000299333.3

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101526 AN: 151970 Hom.: 35806 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.605 AC: 295190 AN: 488168 Hom.: 92053 Cov.: 5 AF XY: 0.611 AC XY: 160961 AN XY: 263330

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.748

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.668 AC: 101636 AN: 152088 Hom.: 35856 Cov.: 32 AF XY: 0.667 AC XY: 49573 AN XY: 74336

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.662

Alfa AF: 0.620 Hom.: 3811

Bravo AF: 0.690

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.65

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: rs1148111; hg19: chr11-123504673;