rs7572423

Positions:

• chr2-166449360-G-A

Variant summary

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

The NM_002976.4(SCN7A):​c.1291-1652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,996 control chromosomes in the GnomAD database, including 6,511 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 0.28 (6511 hom., cov: 31)
• Consequence: SCN7A NM_002976.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN7A	NM_002976.4	c.1291-1652C>T		intron_variant		ENST00000643258.1	NP_002967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN7A	ENST00000643258.1	c.1291-1652C>T		intron_variant			NM_002976.4	ENSP00000496114	P1
SCN7A	ENST00000441411.2	c.1291-1652C>T		intron_variant		1		ENSP00000403846	P1
SCN7A	ENST00000424326.5	c.1291-1652C>T		intron_variant, NMD_transcript_variant		1		ENSP00000396600
SCN7A	ENST00000419992.6	c.1291-1652C>T		intron_variant		5		ENSP00000413699

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42593 AN: 151878 Hom.: 6508 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.280 AC: 42604 AN: 151996 Hom.: 6511 Cov.: 31 AF XY: 0.280 AC XY: 20773 AN XY: 74264

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.296

Alfa AF: 0.308 Hom.: 914

Bravo AF: 0.275

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.29

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

Other links and lift over

dbSNP: rs7572423; hg19: chr2-167305870;