rs13015447

Variant names:

• chr2-166521468-A-C
• rs13015447
• ENST00000650747.1:c.-14-43758T>G

Variant summary

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

The ENST00000650747.1(SCN7A):​c.-14-43758T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,182 control chromosomes in the GnomAD database, including 10,983 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 0.38 (10983 hom., cov: 33)
• Consequence: SCN7A ENST00000650747.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 14 publications found

Genes affected

SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]

LOC124906087 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124906087	XR_007087280.1	n.140+20708A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN7A	ENST00000650747.1	c.-14-43758T>G		intron_variant	Intron 4 of 4			ENSP00000498959.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57026 AN: 152064 Hom.: 10974 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.375 AC: 57073 AN: 152182 Hom.: 10983 Cov.: 33 AF XY: 0.380 AC XY: 28301 AN XY: 74396

African (AFR) AF: 0.343 AC: 14239 AN: 41512

American (AMR) AF: 0.400 AC: 6121 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3262 AN: 5156

South Asian (SAS) AF: 0.277 AC: 1336 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4804 AN: 10600

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24942 AN: 68012

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.374 Hom.: 38052

Bravo AF: 0.374

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.69
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs13015447; hg19: chr2-167377978;