rs7572423

Variant names:

• chr2-166449360-G-A
• rs7572423
• NM_002976.4:c.1291-1652C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002976.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN7A	NM_002976.4	MANE Select	c.1291-1652C>T		intron	N/A	NP_002967.2
	SCN7A	NR_045628.1		n.1421-1652C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN7A	ENST00000643258.1	MANE Select	c.1291-1652C>T		intron	N/A	ENSP00000496114.1
	SCN7A	ENST00000441411.2	TSL:1	c.1291-1652C>T		intron	N/A	ENSP00000403846.2
	SCN7A	ENST00000424326.5	TSL:1	n.1291-1652C>T		intron	N/A	ENSP00000396600.1

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

African (AFR) AF: 0.169 AC: 7011 AN: 41482

American (AMR) AF: 0.339 AC: 5165 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3464

East Asian (EAS) AF: 0.154 AC: 797 AN: 5168

South Asian (SAS) AF: 0.283 AC: 1361 AN: 4808

European-Finnish (FIN) AF: 0.302 AC: 3194 AN: 10570

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23198 AN: 67936

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.303 Hom.: 929

Bravo AF: 0.275

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.29
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7572423; hg19: chr2-167305870;