rs8192613

Variant names:

• chr11-118167098-G-T
• rs8192613
• NM_004588.5:c.449-12C>A

Variant summary

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

The NM_004588.5(SCN2B):​c.449-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,607,468 control chromosomes in the GnomAD database, including 191,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16819 hom., cov: 32)
  • Exomes 𝑓: 0.49 (174712 hom.)
• Consequence: SCN2B NM_004588.5 intron
• Scores: Splicing: ADA: 0.0002714
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.332

Genes affected

SCN2B (HGNC:10589): (sodium voltage-gated channel beta subunit 2) The protein encoded by this gene is the beta 2 subunit of the type II voltage-gated sodium channel. The encoded protein is involved in cell-cell adhesion and cell migration. Defects in this gene can be a cause of Brugada Syndrome, atrial fibrillation, or sudden infant death syndrome. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-118167098-G-T is Benign according to our data. Variant chr11-118167098-G-T is described in ClinVar as [Benign]. Clinvar id is 259446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118167098-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2B	NM_004588.5	c.449-12C>A		intron_variant	Intron 3 of 3	ENST00000278947.6	NP_004579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2B	ENST00000278947.6	c.449-12C>A		intron_variant	Intron 3 of 3	1	NM_004588.5	ENSP00000278947.5
SCN2B	ENST00000658882.1	n.*274-12C>A		intron_variant	Intron 4 of 4			ENSP00000499572.1
SCN2B	ENST00000669850.1	n.691-12C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70140 AN: 151890 Hom.: 16804 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.467

GnomAD3 exomes AF: 0.505 AC: 123691 AN: 244966 Hom.: 32294 AF XY: 0.509 AC XY: 67523 AN XY: 132762

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.543

Gnomad EAS exome AF: 0.776

Gnomad SAS exome AF: 0.550

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.486 AC: 706813 AN: 1455462 Hom.: 174712 Cov.: 40 AF XY: 0.488 AC XY: 353632 AN XY: 724196

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.462 AC: 70195 AN: 152006 Hom.: 16819 Cov.: 32 AF XY: 0.470 AC XY: 34897 AN XY: 74312

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.473

Alfa AF: 0.467 Hom.: 5016

Bravo AF: 0.456

Asia WGS AF: 0.636 AC: 2207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 06, 2016

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Atrial fibrillation, familial, 14 Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.034
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: rs8192613; hg19: chr11-118037813;