chr11-123633290-C-T

Variant names:

• chr11-123633290-C-T
• rs72552198
• NM_001040151.2:c.*509G>A

Variant summary

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

The NM_001040151.2(SCN3B):​c.*509G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 152,280 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN3B NM_001040151.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.550
• Publications: 1 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=-0.81).
• BP6: Variant 11-123633290-C-T is Benign according to our data. Variant chr11-123633290-C-T is described in ClinVar as Benign. ClinVar VariationId is 303187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040151.2. 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.*509G>A		3_prime_UTR	Exon 7 of 7	NP_001035241.1	Q9NY72
	SCN3B	NM_018400.4		c.*509G>A		3_prime_UTR	Exon 6 of 6	NP_060870.1	Q9NY72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.*509G>A		3_prime_UTR	Exon 7 of 7	ENSP00000299333.3	Q9NY72
	SCN3B	ENST00000392770.6	TSL:1	c.*509G>A		3_prime_UTR	Exon 6 of 6	ENSP00000376523.2	Q9NY72
	SCN3B	ENST00000530277.5	TSL:1	c.*853G>A		3_prime_UTR	Exon 6 of 6	ENSP00000432785.1	Q9NY72

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5453 AN: 152162 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0344

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0358 AC: 5459 AN: 152280 Hom.: 135 Cov.: 32 AF XY: 0.0371 AC XY: 2761 AN XY: 74454

African (AFR) AF: 0.0675 AC: 2803 AN: 41540

American (AMR) AF: 0.0542 AC: 829 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.0712 AC: 369 AN: 5180

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4826

European-Finnish (FIN) AF: 0.0206 AC: 219 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 816 AN: 68026

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0238 Hom.: 151

Bravo AF: 0.0397

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	8.5
DANN	Benign	0.72
PhyloP100		0.55
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: rs72552198; hg19: chr11-123503998;