rs13015447

chr2-166521468-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007087280.1(LOC124906087):n.140+20708A>C variant causes a intron, non coding transcript 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: LOC124906087 XR_007087280.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

LOC124906087 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LOC124906087	XR_007087280.1	n.140+20708A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN7A	ENST00000650747.1	c.-14-43758T>G		intron_variant

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

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.373

Alfa AF: 0.375 Hom.: 17326

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13015447; hg19: chr2-167377978;