rs11717455

Variant names:

• chr3-38802156-T-C
• rs11717455
• NM_006514.4:c.-32-8114A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006514.4(SCN10A):​c.-32-8114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,192 control chromosomes in the GnomAD database, including 1,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1192 hom., cov: 32)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 9 publications found

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SCN10A Gene-Disease associations (from GenCC):

• sodium channelopathy-related small fiber neuropathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• episodic pain syndrome, familial, 2

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• Brugada syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.-32-8114A>G		intron_variant	Intron 1 of 27	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.-32-8114A>G		intron_variant	Intron 1 of 27	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000655275.1	c.-12-8134A>G		intron_variant	Intron 1 of 27			ENSP00000499510.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17713 AN: 152074 Hom.: 1192 Cov.: 32

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0751

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17716 AN: 152192 Hom.: 1192 Cov.: 32 AF XY: 0.113 AC XY: 8417 AN XY: 74398

African (AFR) AF: 0.0713 AC: 2960 AN: 41526

American (AMR) AF: 0.133 AC: 2026 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3466

East Asian (EAS) AF: 0.0750 AC: 389 AN: 5184

South Asian (SAS) AF: 0.139 AC: 670 AN: 4820

European-Finnish (FIN) AF: 0.0774 AC: 821 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9991 AN: 67988

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.138 Hom.: 3562

Bravo AF: 0.120

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11717455; hg19: chr3-38843647;