11-123633965-C-G

Variant names:

• chr11-123633965-C-G
• rs1148111
• ENST00000530277.5:c.*178G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000530277.5(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 ENST00000530277.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.139
• Publications: 3 publications found

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]

SCN3B Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome 7

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000530277.5. 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
	SCN3B	NM_001040151.2	MANE Select	c.*22+156G>C		intron	N/A	NP_001035241.1	Q9NY72
	SCN3B	NM_018400.4		c.*22+156G>C		intron	N/A	NP_060870.1	Q9NY72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	ENST00000530277.5	TSL:1	c.*178G>C		3_prime_UTR	Exon 6 of 6	ENSP00000432785.1	Q9NY72
	SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.*22+156G>C		intron	N/A	ENSP00000299333.3	Q9NY72
	SCN3B	ENST00000392770.6	TSL:1	c.*22+156G>C		intron	N/A	ENSP00000376523.2	Q9NY72

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

African (AFR) AF: 0.907 AC: 12988 AN: 14326

American (AMR) AF: 0.601 AC: 18925 AN: 31482

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 10539 AN: 16202

East Asian (EAS) AF: 0.784 AC: 22757 AN: 29022

South Asian (SAS) AF: 0.748 AC: 41519 AN: 55540

European-Finnish (FIN) AF: 0.486 AC: 14686 AN: 30214

Middle Eastern (MID) AF: 0.664 AC: 2379 AN: 3582

European-Non Finnish (NFE) AF: 0.551 AC: 154793 AN: 281028

Other (OTH) AF: 0.620 AC: 16604 AN: 26772

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

African (AFR) AF: 0.905 AC: 37564 AN: 41512

American (AMR) AF: 0.642 AC: 9804 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2231 AN: 3472

East Asian (EAS) AF: 0.750 AC: 3877 AN: 5170

South Asian (SAS) AF: 0.769 AC: 3709 AN: 4824

European-Finnish (FIN) AF: 0.480 AC: 5073 AN: 10564

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37252 AN: 67962

Other (OTH) AF: 0.662 AC: 1394 AN: 2106

Alfa AF: 0.620 Hom.: 3811

Bravo AF: 0.690

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs1148111; hg19: chr11-123504673;