Genetic Variant SCN4B:c.*2497G>A (chr11-118134530-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_174934.4(SCN4B):c.*2497G>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 0.000784 in 454,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

SCN4B
NM_174934.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.499

Variant links:

Genes affected

SCN4B (HGNC:10592): (sodium voltage-gated channel beta subunit 4) The protein encoded by this gene is one of several sodium channel beta subunits. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.[provided by RefSeq, Mar 2009]

SCN4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High AC in GnomAd4 at 256 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCN4B	NM_174934.4 link	c.*2497G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000324727.9	NP_777594.1	Q8IWT1-1B0YJ93
SCN4B	NM_001142349.2 link	c.*2497G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001135821.1	Q8IWT1-2
SCN4B	NM_001142348.2 link	c.*2497G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001135820.1	Q8IWT1-3
SCN4B	NR_024527.2 link	n.3173G>A	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN4B	ENST00000324727 link	c.*2497G>A	3_prime_UTR_variant	Exon 5 of 5	1	NM_174934.4	ENSP00000322460.4	Q8IWT1-1
SCN4B	ENST00000415030.6 link	n.3327G>A	non_coding_transcript_exon_variant	Exon 4 of 4	1
SCN4B	ENST00000423160.2 link	n.2818G>A	non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000529

AC:

AN:

130482

AF XY:

0.000351

show subpopulations

Gnomad AFR exome

AF:

0.00558

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.000331

AC:

100

AN:

301796

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

AN XY:

171996

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

AC:

AN:

8554

Gnomad4 AMR exome

AF:

0.00114

AC:

AN:

27274

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

10786

Gnomad4 EAS exome

AF:

0.000434

AC:

AN:

9210

Gnomad4 SAS exome

AF:

0.000184

AC:

AN:

59650

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

12366

Gnomad4 NFE exome

AF:

0.0000441

AC:

AN:

158764

Gnomad4 Remaining exome

AF:

0.000214

AC:

AN:

14042

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00168

AC:

256

AN:

152288

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00556

AC:

0.00555823

AN:

0.00555823

Gnomad4 AMR

AF:

0.000588

AC:

0.000588235

AN:

0.000588235

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000386

AC:

0.000386399

AN:

0.000386399

Gnomad4 SAS

AF:

0.00145

AC:

0.00144988

AN:

0.00144988

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000588

AC:

0.0000588028

AN:

0.0000588028

Gnomad4 OTH

AF:

0.00142

AC:

0.00141911

AN:

0.00141911

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000769

Hom.:

Bravo

AF:

0.00172

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital long QT syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.4

DANN

Benign

0.40

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over